Abstract:
Alzheimer's disease (AD) and Parkinson's disease (PD) are the predominant neurodegenerative disorders of late life. Both disorders do not form nosological entities. A minority of all AD cases is caused by mutations on chromosomes 1, 14 and 21, a minority of all PD cases by mutations on chromosomes 1, 2, 4, 6 and 12, whereas the majority of all both AD and PD cases is age‐related and sporadic in origin. In sporadic AD, the desensitization of the neural insulin receptor similar to non‐insulin dependent diabetes mellitus may be the core abnormality inducing a cascade‐like process of disturbances in the insulinergic, acetylcholinergic and glutamatergic systems. Cellular glucose metabolism and its derivatives acetylcholine, cholesterol and ATP are most compromised probably inducing abnormalities in the metabolism of the amyloid precursor protein APP and of tau‐protein resulting in the formation of both amyloidiogenic derivatives and hyperphosphorylated tau‐protein. As a result, mental deficits in cognition, learning and memory predominate the clinical feature.
Although mental deficits are also found in the course of PD due to an involvement of the acetylcholinergic system, this disorder starts with movement disturbances due to structural and metabolic abnormalities of nigrostriatal dopaminergic system. Thus, clear differences become obvious between sporadic AO and sporadic PD in their pathophysiologies.
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Abbreviations
- ACTH:
-
adrenocorticotrophic hormone
- AD:
-
Alzheimer's disease
- AGE:
-
advanced glycation endproduct
- APOE:
-
apolipoprotein E
- APP:
-
amyloid precursor protein
- ATP:
-
adenosine triphosphate
- βA4:
-
β-amyloid 4
- CA:
-
cornu ammonis
- CDK:
-
cyclin-dependent kinase
- CNS:
-
central nervous system
- CRF:
-
corticotropic releasing factor
- CSF:
-
cerebrospinal fluid
- DNA:
-
desoxyribonucleic acid
- ER:
-
endoplasmic reticulum
- GA:
-
Golgi apparatus
- GABA:
-
γ-amino butyric acid
- GRP:
-
glucose-regulated protein
- GSK:
-
glycogen synthase kinase
- HPA:
-
hypothalamic-pituitary-adrenal
- HSP:
-
heat shock protein
- IDE:
-
insulin degrading enzyme
- IGF:
-
insulin-like growth factor
- IRS:
-
insulin receptor substrate
- MAP:
-
mitogen-activated protein
- mRNA:
-
messenger ribonucleic acid
- NEK:
-
nuclear factor kappa
- NMDA:
-
N-methyl-D-aspartate
- PD:
-
Parkinson's disease
- PDH:
-
pyruvate dehydrogenase
- PI:
-
phosphatidylinositol
- PS:
-
presenilin
- RAGE:
-
receptor of advanced glycation endproduct
- SAPK/JNK:
-
stress-activated protein kinase/c-Jun N-terminal kinase
- TCAC:
-
tricarboxylic acid cycle
- UDP:
-
uridine diphosphate
References
Abbott MA, Wells DG, Fallon JR. 1999. The insulin receptor tyrosine kinase substrate p 58/53 and the insulin receptor are components of CNS synapses. J Neurosci 19: 7300–7308.
Abeijon C, Hirschberg CB. 1988. Intrinsic membrane glycoproteins with cytosol-orientied sugards in the endoplasmic reticulum. Proc Natl Acad Sci USA 85: 1010–1014.
Adamo M, Raizada MK, Le Roith D. 1989. Insulin and insulin-like growth factor receptors in the nervous system. Mol Neurobiol 3: 71–100.
Adrian GS, McCammon MT, Montgomery DL, Douglas MG. 1986. Sequences required for delivery and localization of the ADP/ATP translocator to the mitochrondrial inner membrane. Mol Cell Biol 6: 626–634.
Ahima RS, Prabakaran D, Mantzoros C, Qu D, Lowell B, et al. 1996. Role of leptin in the neuroendocrine response to fasting. Nature 382: 250–252.
Ahlijanian MK, Barrezueta NX, Williams RD, Jakowski A, Kowsz KP, et al. 2000. Hyperphosphorylated tau and neurofilament and cytoskeletal disruptions in mice overexpressing human p25, an activator of cdk5. Proc Natl Acad Sci USA 97: 2910–2915.
Aisen P, Davis K. 1994. Inflammatory mechanisms in Alzheimer's disease: Implications for therapy. Am J Psychiatry 151: 1105–1113.
Akiyama H, Barger S, Barnum S, Bradt B, Bauer J, et al. 2000. Inflammation and Alzheimer's disease. Neurobiol Aging 21: 393–421.
Akiyama H, Kondo H, Ikeda K, Kato M, McGeer PL. 2001. Immunohistochemical localization of neprilysin in the human cerebral cortex: Inverse association with vulnerability to amyloid β-protein (Aβ) deposition. Brain Res 902: 277–281.
Albert ML, Feldman RG, Willis AL. 1974. The “subcortical dementia” of progressive supranuclear palsy. J Neurol Neurosurg Psychiatry 37: 121–130.
Alessi DR, Cohen P. 1998. Mechanism of activation and function of protein kinase B. Curr Opin Genet Dev 8: 55–62.
Alzheimer A. 1911. Über eigenartige Krankheitsfälle des späteren Alters. Ztschr. ges. Neurol Psychiatry 4: 356–385.
Andrews JM, Terry RD, Spataro J. 1970. Striatonigral degeneration. Clinical-pathological correlations and response to stereotaxic surgery. Arch Neurol 23: 319–239.
Apelt J, Ach K, Schliebs R. 2003. Aging-related down-regulation of neprilysin, a putative β-amyloid-degrading enzyme, in transgenic Tg2576 Alzheimer-like mouse brain is accompanied by an astroglial upregulation in the vicinity of β-amyloid plaques. Neurosci Lett 339: 182–186.
Apelt J, Mehlhorn G, Schliebs R. 1999. Insulin-sensitive GLUT 4 glucose transporters are localized with GLUT 3-expressing cells and demonstrate a chemically distinct neuron-specific localization in rat brain. J Neurosci Res 57: 693–705.
Apelt J, Schliebs R. 2001. β-Amyloid-induced glial expression of both pro- and anti-inflammatory cytokines in cerebral cortex of aged transgenic Tg2576 mice with Alzheimer plaque pathology. Brain Res 894: 21–30.
Aplin AE, Gibb GM, Jacobsen JS, Gallo JM, Anderton BH. 1996. In vitro phosphorylation of the cytoplasmic domain of the amyloid precursor protein by glycogen synthase kinase-3β. J Neurochem 67: 699–707.
Arai H, Lee VMY, Messinger ML, Greenberg BD, Lowery DE, et al. 1991. Expression of pattern of β-amyloid precursor protein (β-APP) in neural and nonneuronal human tissues from Alzheimer's disease and control subjects. Ann Neurol 30: 686–693.
Arendt T. 2003. Synaptic plasticity and cell cycle activation in neurons are alternative effector pathways: The ‘Dr. Jekyll and Mr. Hyde concept’ of Alzheimer's disease or the yin and yang of neuroplasticity. Prog Neurobiol 71: 83–248.
Arias C, Montiel T, Quiroz-Baez R, Massieu L. 2002. β-Amyloid neurotoxicity is exacerbated during glycolysis inhibition and mitochondria impairment in the rat hippocampus in vivo and in isolated nerve terminals: Implications for Alzheimer's disease. Exp Neurol 176: 163–174.
Arnaiz E, Jelic V, Almkvist O, Wahlund LO, Winblad B, et al. 2001. Impaired cerebral glucose metabolism and cognitive functioning predict deterioration in mild cognitive impairment. Neuroreport 12: 851–855.
Ashford ML, Boden PR, Treherne JM. 1990. Glucose-induced excitation of hypothalamic neurons is mediated by ATP-sensitive K+ channels. Pflügers Arch 415: 479–483.
Atanasov AG, Nashev LG, Schweizer RAS, Frick C, Odermatt A. 2004. Hexose-6 phosphate dehydrogenase determines the reaction direction of 11β-hydroxysteroid dehydrogenase type 1 as an oxoreductase. FEBS Lett 571: 129–133.
Avruch J. 1998. Insulin signal transduction through protein kinase cascades. Mol Cell Biochem 182: 31–48.
Bachelard HS. 1971. Specific and kinetic properties of monosaccharide uptake into guinea pig cerebral cortex in vitro. J Neurochem 13: 213–222.
Bak P, Tang C, Wiesenfeld K. 1988. Self-organized criticality. Physic Rev A 38: 365–374.
Baltes PB, Mayer KU, Helmchen H, Steinhagen-Thiessen E. 1999. The Berlin Aging Study (BASE): Sample, Design, and Overviews of Measures. Baltes PB, Mayer KU, editors. Cambridge: Cambridge University Press; pp. 15–55.
Banhegyi G, Benedetti A, Fulceri R, Senesi S. 2004. Cooperativity between 11β-hydroxysteroid dehydrogenase type 1 and hexose-6-phosphate dehydrogenase in the lumen of the endoplasmic reticulum. J Biol Chem 279: 27017–27021.
Banks WA. 2004. The source of cerebral insulin. Eur J Pharmacol 490: 5–12.
Baskin DG, Brewitt B, Davidson DA, Crop E, Paquette T, et al. 1986. Quantitative autoradiographic evidence for insulin receptors in the choroid plexus of the rat brain. Diabetes 35: 246–249.
Baskin DG, Schwartz MW, Sipols AJ, D'Alessio DA, Goldstein BJ, et al. 1994. Insulin receptor substrate-1 (IRS-1) expression in rat brain. Endocrinology 134: 1952–1955.
Baskin DG, Sipols AJ, Schwartz MW, White MF. 1993. Immunocytochemical detection of insulin receptor substrate-1(IRS-1) in rat brain: Colocalization with phosphotyrosine. Regul Pept 48: 257–266.
Baskin DS, Browning JL, Pirozzollo FJ, Korporaal S, Baskin JA, et al. 1999. Brain choline acetyltransferase and mental function in Alzheimer disease. Arch Neurol 56: 1221–1223.
Baudry M, Arst DS, Lynch G. 1981. Increased (3H) glutamate receptor binding in aged rats. Brain Res 223: 195–198.
Beach TG, Walker DG, Cynader MS, Hughes LH. 1996. Increased β-amyloid precursor protein mRNA in the rat cerebral cortex and hippocampus after chronic systemic atropine treatment. Neurosci Lett 210: 13–16.
Beach TG, Walker R, McGeer EG. 1989. Patterns of gliosis in Alzheimer's disease and aging cerebrum. Glia 2: 420–436.
Belanoff JK, Gross K, Yager A, Schatzberg AF. 2001. Corticosteroids and cognition. J Psychiatric Res 35: 127–145.
Bennecib M, Gong CX, Grundke-Iqbal I, Iqbal K. 2000. Role of protein phosphatase-2A and -1 in the regulation of GSK-3, cdk 5 and cdc 2 and the phosphorylation of tau in rat forebrain. FEBS Lett 485: 87–93.
Benzi G, Pastoris O, Villa RF, Giuffrida-Stella AM. 1984. Effect of aging on cerebral cortex energy metabolism in hypoglycemia and posthypoglycemic recovery. Neurobiol Aging 5: 457–463.
Bernardi H, Fosset M, Lazdunski M. 1988. Characterization, purification, and affinity labeling of the brain (3H) glibenclamide-binding protein, a putative neuronal ATP-regulated K + channel. Proc Natl Acad Sci USA 85: 9816–9820.
Bernstein HG, Ansorge S, Riederer P, Reiser FM, Frölich L, et al. 1999. Insulin-degrading enzyme in Alzheimer's disease brain: Prominent localization in neurons and senile plaques. Neurosci Lett 263: 161–164.
Bhat RV, Shanley J, Correll MP, Fieles WE, Keith RA, et al. 2000. Regulation and localization of tyrosine216 phosphorylation of glycogen synthase kinase-3β in cellular and animal models of neuronal degeneration. Proc Natl Acad Sci USA 97: 11074–11079.
Bierhaus A, Wolf J, Andrassy M, Rohleder N, Humpert PM, et al. 2003. A mechanism converting psychosocial stress into mononuclear cell activation. Proc Natl Acad Sci USA 100: 1920–1925.
Bigl M, Apelt J, Eschrich K, Schliebs R. 2003. Cortical glucose metabolism is altered in aged transgenic Tg 2576 mice that demonstrate Alzheimer plaque pathology. J Neural Transm 110: 77–94.
Bigl M, Beck M, Bleyl AD, Bigl V, Eschrich K. 2000. Altered prosphofructokinase mRNA levels but unchanged isoenzyme pattern in brains from patients with Alzheimer's diseae. Mol Brain Res 76: 411–414.
Bigl M, Bleyl AD, Zedlick D, Arendt T, Bigl V, et al. 1996. Changes of activity and isoenzyme pattern of phosphofructokinase in the brains of patients with Alzheimer's disease. J Neurochem 67: 1164–1171.
Bigl M, Brückner MK, Arendt T, Bigl V, Eschrich K. 1999. Activities of key glycolytic enzymes in the brains of patients with Alzheimer's disease. J Neural Transm 106: 499–511.
Bigl V, Arendt T, Fischer S, Werner M, Arendt A. 1987. The cholinergic system in aging. Gerontology 33: 172–180.
Bigl V, Schliebs R. 1998. Simulation of cortical cholinergic deficits: A novel experimental approach to study pathogenetic aspects of Alzheimer's disease. J Neural Transm (Suppl. 54): 237–247.
Blass JP, Gibson GE, Hoyer S. 2002. The role of the metabolic lesion in Alzheimer's disease. J Alzheimer Dis 4: 225–232.
Blusztajn JK, Lopez Gonzales-Coviella I, Logue M, Growdon JH, Wurtman RJ. 1990. Levels of phospholipid catabolic intermediates, glycerophosphocholine and glycerophosphoethanolamine, are elevated in brains of Alzheimer's disease but not of Down's syndrome patients. Brain Res 536: 240–244.
Boado RJ. 1995. Brain-derived peptides regulate the steady state levels and increase stability of the blood-brain barrier GLUT-1 glucose transporter mRNA. Neurosci Lett 197: 179–182.
Bole DG, Dowin R, Doriaux M, Jamieson JD. 1989. Immunocytochemical localization of BiP to the rough endoplasmic reticulum: Evidence for protein sorting by selective retention. J Histochem Cytochem 37: 1817–1823.
Borit A, Rubinstein LJ, Urich H. 1975. The striatonigral degenerations: Putaminal pigments and nosology. Brain 98: 101–112.
Born J, Lange T, Kern W, McGregor GP, Bickel U, et al. 2002. Sniffing neuropeptides: A transnasal approach to the human brain. Nat Neurosci 5: 514–516.
Bosboom JLW, Stoffers D, Wolters EC. 2004. Cognitive dysfunction and dementia in Parkinson's disease. J Neural Transm 111: 1303–1315.
Bowen DM. 1984. Cellular aging: Selective vulnerability of cholinergic neurons in human brain. Monogr Dev Biol 17: 42–59.
Braakman I, Helenius J, Helenius A. 1992. Role of ATP and disulfide bonds during protein folding in the endoplasmic reticulum. Nature 356: 260–261.
Brant AM, Jess TJ, Milligan G, Brown CM, Gould GW. 1993. Immunological analysis of glucose transporters expressed in different regions of the rat brain and central nervous system. Biochem Biophys Res Commun 192: 1297–1302.
Brett J, Schmidt AM, Yan SD, Zou YD, Weidman E, et al. 1993. Survey of the distribution of an newly characterized receptor for advanced glycation end products in tissues. Am J Pathol 143: 1699–1712.
Brown GG, Levine SR, Gorell JM, Pettegrew JW, Gdowski JE, et al. 1989. In vitro 31P-NMR profiles of Alzheimer disease and multiple subcortical infarct dementia. Neurology 39: 1423–1427.
Brun A, Englund E. 1981. Regional pattern of degeneration in Alzheimer's disease: Neuronal loss and histopathological grading. Histopathology 5: 549–564.
Bucht G, Adolfsson R, Lithner F, Winblad B. 1983. Changes in blood glucose and insulin secretion in patients with senile dementia of Alzheimer type. Acta Med Scand 213: 387–392.
Buse MG, Robinson KA, Marshall BA, Hresko RC, Mueckler MM. 2002. Enhanced O-GlcNAc protein modification is associated with insulin resistance in GLUT1-overexpressing muscles. Am J Physiol Endocrinol Metab 283: E241–E250.
Buttgereit F, Brand MD. 1995. A hierarchy of ATP-consuming processes in mammalian cells. Biochem J 312: 163–167.
Buxbaum JD, Koo EH, Greengard P. 1993. Protein phosphorylation inhibits production of Alzheimer amyloid β/A4 peptide. Proc Natl Acad Sci USA 90: 9195–9198.
Capasso JM, Abeijon C, Hirschberg CB. 1988. An intrinsic membrane glycoprotein of the Golgi apparatus with O-linked N-acetylglucosamine facing the cytosol. J Biol Chem 263: 19778–19782.
Carney JM, Starke-Reed PE, Oliver CN, Landum RW, Cheng MS, et al. 1991. Reversal and -age-related increase in brain protein oxidation, decrease in enzyme activity, and loss in temporal and spatial memory by chronic administration of the spin-trapping compound N-tert-butyl-alpha-phenylnitrone. Proc Natl Acad Sci USA 88: 3633–3636.
Carson JA, Turner AJ. 2002. Beta-amyloid catabolism: Roles for neprilysin (NP) and other metallopeptidases? J Neurochem 81: 1–8.
Chen YZ. 2004. APP induces neuronal apoptosis through APP-BP1-mediated downregulation of beta-catenin. Apoptosis 9: 415–422.
Chiarugi A. 2002. Characterization of the molecular events following impairment of NF-kB-driven transcription in neurons. Mol Brain Res 109: 179–188.
Cho KS, Choi J, Ha CM, Son YJ, Choi WS, et al. 2002. Comparison of gene expression in old versus young rat hippocampus by cDNA array. Neuro Report 13: 285–289.
Chou CK, Dull TJ, Russel DS, Gherzi R, Lebwohl D, et al. 1987. Human insulin receptors mutated at the ATP-binding site lack protein tyrosine activity and fail to mediate postreceptor effects of insulin. J Biol Chem 262: 1842–1847.
Chrousos GP, Gold PW. 1992. The concept of stress and stress system disorders. J Am Med Assoc 267: 1244–1252.
Ciechanover A, Brundin P. 2003. The ubiquitoin proteasome system in neurodegenerative diseases: Sometomes the chicken, sometimes the egg. Neuron 40: 427–446.
Cizza G, Calogero AE, Brady LS, Bagdy G, Bergamini E, et al. 1994. Male Fischer 344/rats show a progressiv impairmaint of the hypothalamic-pituitary-adrenal axis with advancing age. Endocrinology 134: 1611–1620.
Cizza G, Gold PW, Chrousos GP. 1995. Aging is associated in the 344/N Fischer rat with decreased stress responsitivity of central and peripheral catecholaminergic systems and impairment of the hypothalamic-pituitary-adrenal axis. Ann N Y Acad Sci 771: 491–511.
Cohen P, Frame S. 2001. The renaissance of GSK. Mol Cell Biol 2: 769–776.
Comer FI, Hart GW. 2001. Reciprocity between 0-GlcNac and 0-phosphate on the carboxyl terminal domain of RNA polymerase II. Biochemistry 40: 7845–7852.
Conejo R, Lorenzo M. 2001. Insulin signalling leading to proliferation, survival and membrane ruffling in C2 C12 myoblasts. J Cell Physiol 187: 96–108.
Conejo R, Valverde AM, Benito M, Lorenzo M. 2001. Insulin produces myogenesis in C2 C12 myoblasts by induction of NF-kappa B and downregulation of AP-1 activities. J Cell Physiol 186: 82–94.
Connell-Crowley L, Le Gall M, Vo DJ, Giniger E. 2000. The cyclin dependent kinase Cdk5 controls multiple aspects of axon patterning in vivo. Curr Biol 10: 599–602.
Convit A, Wolf OT, Tarshish C, de Leon MJ. 2003. Reduced glucose tolerance is associated with poor memory performance and hippocampal atrophy among normal elderly. Proc Natl Acad Sci USA 100: 2019–2022.
Cook DG, Forman FS, Sung IC, Leight S, Kolson DI, et al. 1997. Alzheimer's Aβ (1–42) is generated in the endoplasmic reticulum/intermediate compartment of NT2N cells. Nat Med 3: 1021–1023.
Cook DG, Leverenz JB, McMillan PJ, Kulstad JJ, Ericksen S, et al. 2003. Reduced hippocampal insulin-degrading enzyme in late-onset Alzheimer's disease is associated with the apolipoprotein E-Σ4 allele. Am J Pathol 162: 313–319.
Cotman CW, Monaghan DT, Ottersen OP, Storm-Mathisen H. 1987. Anatomical organization of excitatory amino acid receptors and their pathways. Trends Neurosci 10: 273–280.
Cotrina ML, Nedergaard M. 2002. Astrocytes in the aging brain. J Neurosci Res 67: 1–10.
Craft S, Asthana S, Schellenberg G, Cherrier M, Baker LD, et al. 1999. Insulin metabolism in Alzheimer'disease differs according to apolipoprotein E genotype and gender. Neuroendocrinology 70: 146–152.
Craft S, Peskind E, Asthana S, Watson GS, Baker LD, et al. 2000. Effects of insulin on cerebrospinal fluid levels of Aβ 42. Neurobiol Aging 21: S272 (1245).
Craft S, Peskind E, Schwartz MW, Schellenberg GD, Raskind M, et al. 1998. Cerebrospinal fluid and plasma insulin levels in Alzheimer's disease: Relationship to severity of dementia and apolipoprotein E genotype. Neurology 50: 164–168.
Crain BJ, Burger PC. 1988. The laminar distribution of neuritic plaques in the fascia dentate of patients with Alzheimer's disease. Acta Neuropathol 76: 86–93.
Cross DA, Watt PW, Shaw M, Kaay von der J, Downes CP, et al. 1997. Insulin activates protein kinase B, inhibits glycogen synthase kinase-3 and activatives glycogen synthase by rapamycin-sensitive pathways in skeletal muscle and adipose tissue. FEBS Lett 406: 211–215.
Cross DAE, Alessi DR, Cohen P, Andjelkovich M, Hemmings BA. 1995. Inhibition of glycogen synthase kinase-3 by insulin mediated protein kinase. Nature 378: 785–789.
Cruz JC, Tseng HC, Goldman JA, Shih H, Tsai LH. 2003. Aberrant cdk5 activation by p25 triggers pathological events leading to neurodegeneration and neurofibrillary tangles. Neuron 40: 471–483.
D'Andrea MR, Cole GM, Ard MD. 2004. The microglial phagocytic role with specific plaque types in the Alzheimer disease brain. Neurobiol Aging 25: 675–683.
D'Andrea MR, Nagele RG, Wang HY, Peterson PA, Lee DHS. 2001. Evidence that neurones accumulating amyloid can undergo lysis to form amyloid plaques in Alzheimer's disease. Histopathology 38: 120–134.
Das S, Potter H. 1995. Expression of the Alzheimer amyloid-promoting factor antichymotrypsin is induced in human astrocytes by IL-1. Neuron 14: 447–456.
Dastur DK. 1985. Cerebral blood flow and metabolism in normal human aging, pathological aging, and senile dementia. J Cereb Blood Flow Metab 5: 1–9.
Davidsson P, Bogdanovic N, Lannfelt L, Blennow K. 2001. Reduced expression of amyloid precursor protein, presenilin-1 and rab 3a in cortical brain regions in Alzheimer's disease. Dement Geriatr Cogn Disord 12: 243–250.
Davies SG, McBean JG, Roberts PJ. 1984. A glutamatergic innervation of the nucleus basalis/substantia innominata. Neurosci Lett 45: 105–110.
Davis KL, Davis BM, Greenwald BS, Mohs RC, Mathé AA, et al. 1986. Cortisol and Alzheimer's disease, I: Basal studies. Am J Psychiatry 143: 300–305.
de Bruin VMS, Vieira MCM, Rocha MNM, Viana GSP. 2002. Cortisol and dehydroepiandrosterone sulfate plasma levels and their relationship to aging, cognitive function, and dementia. Brain Cogn 50: 316–323.
de Kloet ER. 1991. Brain corticosteroid receptor balance and homeostatic control. Front Neuroendocrinol 12: 95–165.
de Quervain DJF, Poirier R, Wollmer MA, Grimaldi LME, Tsolaki M, et al. 2004. Glucocorticoid-related genetic susceptibility for Alzheimer's disease. Human Mol Genet 13: 47–52.
Degrell I, Krier C, Hoyer S. 1993. Neuropathology and Neuropharmacology. Aging, Vol 21. Cervos-Navarro J, Sarkander MI, editors. New York; Raven; pp. 289–300.
Dekker MC, Bonifati V, van Duijn CM. 2003. Parkinson's disease: Piecing together a genetic jigsaw. Brain 126: 1722–1733.
Demaurex N, Furuya W, D'Souza S, Bonifacino JS, Grinstein S. 1998. Mechanism of acidification of the trans-Golgi network (TGN). In situ measurements of pH using retrieval of TGN 38 and furin from the cell surface. J Biol Chem 273: 2044–2051.
Devaskar SU, Giddings SJ, Rajakumar PA, Carnaghi LR, Menon RK, et al. 1994. Insulin gene expression and insulin synthesis in mammalian neuronal cells. J Biol Chem 269: 8445–8454.
Dickson D, Lee S, Mattiace L, Yen S, Brosnan C. 1993. Microglia and cytokines in neurological disease, with specific reference to AIDS and Alzheimer's disease. Glia 7: 75–83.
Dickson D, Rogers J. 1992. Neuroimmunology of Alzheimer's disease. Neurobiol Aging 15: 793–798.
Dorner AJ, Wasley LC, Kaufman RJ. 1990. Protein dissociation from GRP78 and secretion are blocked by depletion of cellular ATP levels. Proc Natl Acad Sci USA 87: 7429–7432.
Drachman DA, Noffsinger D, Sahakian BJ, Kurdziel S, Fleming P. 1980. Aging, memory and the cholinergic system: A study of dichotic listening. Neurobiol Aging 1: 39–43.
Duara R, Grady C, Haxby J, Sundaram S, Cutler NR, et al. 1986. Positron emission tomography in Alzheimer's disease. Neurology 36: 879–887.
Duax WL, Griffin JF, Ghosh D. 1996. The fascinating complexities of steroid-binding enzymes. Curr Opin Struct Biol 6: 813–823.
Dubelaar EJG, Verwer RWH, Hofman MA, van Heerikhuize JJ, Ravid R, et al. 2004. ApoE Σ4 genotype is accompanied by lower metabolic activity in nucleus basalis of Meynert neurons in Alzheimer patients and controls as indicated by the size of Golgi apparatus. J Neuropathol Exp Neurol 63: 159–169.
Duckworth WC. 1988. Insulin degradation: Mechanisms, products and significance. Endocr Rev 9: 319–345.
Dunn-Meynell AA, Routh VH, McArdle JJ, Levin BE. 1997. Low affinity sulfonylurea binding sites reside on neuronal cell bodies in the brain. Brain Res 745: 1–9.
Dutschke K, Nitsch RM, Hoyer S. 1994. Short-term mental activation accelerates the age-related decline of high-energy phosphates in rat cerebral cortex. Arch Gerontol Geriatr 19: 43–51.
Ebadi M, Govitrapong P, Sharma S, Murali-Krishan D, Shavali S, et al. 2001. Ubiquinone (coenzyme q10) and mitochondria in oxidative stress of Parkinson's disease. Biol Signals Recept 10: 224–253.
Eckert GP, Cairns NJ, Maras A, Gattaz WF, Müller WE. 2000. Cholesterol modulates the membrane-disordering effects of beta-amyloid peptides in the hippocampus: Specific changes in Alzheimer's disease. Demen Geriatr Cogn Disord 11: 181–186.
Edland SD, Wavrant-De Vriesé F, Compton D, Smith GE, Ivnik R, et al. 2003. Insulin degrading enzyme (IDE) genetic variants and risk of Alzheimer's disease: Evidence of effect modification by apolipoprotein E (APOE). Neurosci Lett 345: 21–24.
Efthimiopoulos S, Punj S, Manolopoulos V, Pangalos M, Wang GP, et al. 1996. Intracellular cyclic AMP inhibits constitutive and phorbol ester-stimulated secretory cleavage of amyloid precursor protein. J Neurochem 67: 872–875.
Eikelenboom P, van Gool WA. 2004. Neuroinflammatory perspectives on the two faces of Alzheimer's disease. J Neural Transm 111: 281–294.
Eikelenboom P, Zhan SS, van Gool WA, Eikelenboom P. 1994. Inflammatory mechanisms in Alzheimer's disease. Trends Pharmacol Sci 15: 147–150.
Eisenberg S, Seltzer HS. 1962. The cerebral metabolic effects of acutely induced hypoglycaemia in human subjects. Metabolism 11: 1162–1168.
El Tamer A, Raikoff K, Hanin I. 1998. Effect of glucose-deprivation on amyloid precursor protein (APP) release from hippocampal (HIP) slices of rat. Soc Neurosci Abstr 24.
Erecinska M, Silver IA. 1989. ATP and brain function. J Cereb Blood Flow Metab 9: 2–19.
Evans DA, Funkenstein H, Albert MS, Scherr PA, Cook NR, et al. 1989. Prevalence of Alzheimer's disease in a community population of older persons: Higher than previously reported. J Am Med Assoc 262: 2551–2556.
Fagiolo U, Cossarizza A, Scala E, Fanales Belasio E, Ortolani C, et al. 1993. Increased cytokine production in mononuclear cells of healthy elderly people. Eur J Immunol 23: 2375–2378.
Fang X, Yu SX, Lu Y, Bast RC Jr, Woodgett JR, et al. 2000. Phosphorylation and inactivation of glycogen synthase kinase 3 by protein kinase A. Proc Natl Acad Sci USA 97: 11960–11965.
Farrell CL, Pardridge WM. 1991. Blood-brain barrier glucose transporter is asymmetrically distributed on brain capillary endothelial luminal and ablumenal membranes: An electron microscopic immunogold study. Proc Natl Acad Sci USA 88: 5779–5783.
Farris W, Mansourian S, Chang Y, Lindsay L, Eckman EA, et al. 2003. Insulin-degrading enzyme regulates the levels of insulin, amlyoid-β protein, and the β-amyloid precursor protein intracellular domain in vivo. Proc Natl Acad Sci USA 100: 4162–4167.
Fearnley JM, Lees AJ. 1991. Aging and Parkinson's disease: Substantia nigra regional selectively. Brain 114: 2283–2301.
Feinstein R, Kanety H, Papa MZ, Lunenfeld B, Karasik A. 1993. Tumor necrosis factor-α suppresses insulin-induced tyrosine phosphorylation of insulin receptor and its substrates. J Biol Chem 268: 26055–26058.
Ferrer I, Blanco R, Carmona M, Puig B. 2001. Phosphorylated mitogen-activated protein kinase (MAPK/ERK-P), protein kinase of 38 kDa (p38-P), stress activated protein kinase (SAPK/JNK-P), and calcium/calmodulin-dependent kinase II (CaMkinase II) are differently expressed in tau deposits in neurons and glial cells in tauopathies. J Neural Transm 108: 1397–1415.
Fillenz M, Lowry JP. 1998. Studies of the source of glucose in the extracellular compartment of the rat brain. J Dev Neurosci 20: 365–368.
Folbergrova J, Ljunggren B, Siesjö BK. 1974. Influence of complete ischemia on glycolytic metabolites of complete ischemia on glycolytic metabolites, citric and cycle intermediates, and associated amino acids in the rat cerebral cortex. Brain Res 80: 265–279.
Foster NL, Chase TN, Mansi K, Brooks R, Fedio P, et al. 1984. Cortical abnormalities in Alzheimer's disease. Ann Neurol 16: 649–654.
Frame S, Cohen P. 2001. GSK 3 takes centre stage more than 20 years after its discovery. Biochem J 359: 1–16.
Frölich L. 2002. The cholinergic pathology in Alzheimer's disease: Discrepancies between clinical experience and pathophysiological findings. J Neural Transm 109: 1003–1014.
Frölich L, Blum-Degen D, Bernstein HG, Engelsberger S, Humrich J, et al. 1998. Insulin and insulin receptors in the brain in aging and sporadic Alzheimer's disease. J Neural Transm 105: 423–438.
Fukami S, Watanabe K, Iwata N, Haraoka H, Lu B, et al. 2002. Aβ-degrading endopeptidase, neprilysin, in mouse brain: Synaptic and axonal localization inversely correlating with Aβ pathology. Neurosci Res 43: 39–56.
Fukuyama H, Ogawa M, Yamauchi H, Yamaguchi S, Kimura J, et al. 1994. Altered cerebral energy metabolism in Alzheimer's disease: A PET study. J Nucl Med 35: 1–6.
Garland PB, Newsholme EA, Randle PJ. 1964. Regulation of glucose uptake by muscle. 9. Effects of fatty acids and ketone bodies, and of alloxan-diabetes and starvation, on pyruvate metabolism and lactate/pyruvate and L-glycerol-3-phosphate/ dihydro- xyacetone phosphate concentration ratios in the heart and rat diaphragm muscles. Biochem J 93: 665–678.
Garland PB, Randle PJ. 1964. Control of pyruvate dehydrogenase in the perfused rat heart by the intracellular concentration of acetyl-coenzyme A. Biochem J 91: 76C–77C.
Garriga J, Cusso R. 1992. Effect of starvation on glycogen and glucose metabolism in different areas of the brain. Brain Res 591: 277–282.
Gasic GP, Heinemann S. 1991. Receptors coupled to ionic channels: The glutamate receptor family. Curr Opin Neurobiol 1: 20–26.
Gasparini L, Gouras GK, Wang R, Gross RS, Beal MF, et al. 2001. Stimulation of β-amyloid precursor protein trafficking by insulin reduces intraneural β-amyloid and requires mitogen-activated protein kinase signalling. J Neurosci 21: 2561–2570.
Gerozissis R, Rouch C, Lemiere S, Nicolaidis S, Orosco M. 2001. A potential role of central insulin in learning and memory related to feeding. Cell Mol Neurobiol 21: 389–401.
Gething MJ, Sambrook J. 1992. Protein folding in the cell. Nature 355: 33–45.
Ghidoni R, Gasparini K, Alberici A, Benussi L, Barbiero L, et al. 2003. Inhibition of energy metabolism down-regulates the Alzheimer related presenilin 2 gene. J Neural Transm 110: 1029–1039.
Gibb WRG, Lees AJ. 1988. The relevance of the Lewy body to the pathogenesis of idiopathic Parkinson's disease. J Neurol Neurosurg Psychiatry 51: 745–752.
Gibbs EL, Lennox WG, Nims LF, Gibbs FA. 1942. Arterial and cerebral venous blood: Arterial venous differences in man. J Biol Chem 144: 325–332.
Gibson GE, Jope R, Blass JP. 1975. Decreased synthesis of acetylcholine accompanying impaired oxidation of pyruvic acid in rat brain minces. Biochem J 148: 17–23.
Gibson GE, Petersen C, Jand enden DJ. 1981. Brain acetylcholine synthesis declines with senescence. Science 213: 674–676.
Gillespie SL, Golde TE, Younkin SG. 1992. Secretory processing of the Alzheimer amyloid β/A4 protein precursor is increased by protein phosphorylation. Biochem Biophys Res Commun 187: 1285–1290.
Giorgino F, Almahfouz A, Goodyear LJ, Smith RJ. 1993. Glucocorticoid regulation of insulin receptor and subtrate IRS-1 tyrosine phosphorylation in rat skeletal muscle in vivo. J Clin Invest 91: 2020–2030.
Goldstein BJ. 1993. Regulation of insulin receptor signalling by protein-tyrosine dephosphorylation. Receptor 3: 1–15.
Gong CX, Grundke-Iqbal I, Iqbal K. 1994a. Dephosphorylation of Alzheimer's disease abnormally phosphorylated tau by protein phosphatase-2A. Neuroscience 61: 765–772.
Gong CX, Lidsky T, Wegiel J, Zuck L, Grundke-Iqbal I, et al. 2000. Phosphorylation of microtubule-associated protein tau is regulated by protein phosphatase 2A in mammalian brain: Implications for neurofibrillary degeneration in Alzheimer's disease. J Biol Chem 275: 5535–5544.
Gong CX, Singh TJ, Grundke-Iqbal I, Iqbal K. 1994b. Alzheimer's disease abnormally phosphorylated tau is dephosphorylated by phosphatase-2B (calcineurin). J Neurochem 62: 803–806.
Gopalakrishan M, Janis RA, Triggle DJ. 1993. ATP-sensitive K+ channels: Pharmacologic properties, regulation, and therapeutic potential. Drug Dev Res 28: 95–127.
Gottstein U, Bernsmeier A, Sedlmeyer I. 1963. Der Kohlenhydratstoffwechsel des menschlichen Gehirns. I. Untersuchungen mit substratspezifischen enzymatischen Methoden bei normaler Hirndurchblutung. Klin Wschr 41: 943–948.
Gottstein U, Held K. 1967. Insulinwirkung auf den menschlichen Hirnmetabolismus unter dem Einfluss intravenöser Infusionen von Glukose Glukagon und Glukose-Insulin. Klin Wschr 43: 965–975.
Gottstein U, Müller W, Berhoff W, Gärtner H, Held K. 1971. Zur Utilisation von nicht-veresterten Fettsäuren und Ketonkörper im Gehirn des Menschen. Klin Wschr 49: 406–411.
Götz ME, Kunig G, Riederer P, Youdim MB. 1994. Oxidative stress: Free radical production in neuronal degeneration. Pharmacol Ther 63: 37–122.
Gouras GK, Tsai J, Naslund J, Vincent B, Edgard M, et al. 2000. Intraneuronal βA42 accumulation in human brain. Am J Pathol 156: 15–20.
Greenfield JP, Tsai J, Gouras GK, Hai B, Thinakaran G, et al. 1999. Endoplasmic reticulum and trans-Golgi network generate distinct populations of Alzheimer β-amyloid peptides. Proc Natl Acad Sci USA 96: 742–747.
Griffith LS, Mathes M, Schmitz B. 1995. β-amyloid precursor protein is modified with O-linked N-acetylglucosamine. J Neurosci Res 41: 270–278.
Griffith LS, Schmitz B. 1995. O-linked N-acetylglucosamine is upregulated in Alzheimer brains. Biochem Biophys Res Commun 213: 423–431.
Grünblatt E, Hoyer S, Riederer P. Changes in gene expression in brain cortex and striatum of the streptozotocin rat model for sporadic Alzheimer's disease (in preparation).
Grünblatt E, Hoyer S, Riederer P. 2004a. Gene expression profile in streptozotocin rat model for sporadic Alzheimer's disease. J Neural Transm 111: 367–386.
Grünblatt E, Mandel S, Jacob-Hirsch J, Zeligson S, Amariglo N, et al. 2004b. Gene expression profiling of parkinsonian substantia nigra pars compacta; alterations in ubiquitin-proteaseome, heat shock protein, iron and oxidative stress regulated proteins, cell adhesion/cellular matrix and vesicle trafficking genes. J Neural Transm 111: 1543–1573.
Gsell W, Jungkunz G, Riederer P. 2004. Functional neurochemistry of Alzheimer's disease. Curr Pharm Design 10: 265–293.
Gsell W, Strein I, Riederer P. 1996. The neurochemistry of Alzheimer type, vascular type and mixed type dementia compared. J Neural Transm 47: 73–101.
Gust DA, Wilson ME, Stocker T, Conrad S, Plotsky PM, et al. 2000. Activity of the hypothalamic-pituitary-adrenal axis is altered by aging and exposure to social stress in female rhesus monkeys. J Clin Endocrinol Metab 85: 2256–2563.
Haass C, Lemere CA, Capell A, Citron M, Seubert P, et al. 1995. The Swedish mutation causes early-onset Alzheimer's disease bei β-secretase cleavage within the secretory pathway. Nat Med 1: 1291–1296.
Haass C, Schlossmacher M, Hung A, Vigo-Pelfrey C, Mellon A, et al. 1992. Amyloid β-peptide is produced by cultured cells during normal metabolism. Nature 359: 322–324.
Halbreich U, Asnis GM, Zumoff B, Nathan RS, Shindledecker R. 1984. Effect of age and sex on cortisol secretion in depressives and normals. Psychiatry Res 13: 221–229.
Hamos JE, Oblas B, Pulaski-Salo D, Welch WJ, Bole DG, et al. 1991. Expression of heat shock proteins in Alzheimer's disease. Neurology 41: 345–350.
Hanger DP, Hughes K, Woodgett JR, Brion JP, Anderton BH. 1992. Glycogen synthase kinase-3 induces Alzheimer's disease-like phosphorylation of tau: Generation of paired helical filament epitopes and neuronal localisation of the kinase. Neurosci Lett 147: 58–62.
Hardy J, Selkoe DJ. 2002. The amyloid hypothesis of Alzheimer's disease: Progress and problems on the road of therapeutics. Science 297: 353–356.
Harik SI, McCracken KA. 1986. Age-related increase in presynaptic noradrenergic markers of the rat cerebral cortex. Brain Res 381: 125–130.
Häring HU. 1991. The insulin receptor: Signalling mechanism and contribution to the pathogenesis of insulin resistance. Diabetologica 34: 848–861.
Häring HU, Kirsch D, Obermeier B, Ermel B, Machicao F. 1986. Decreased tyrosine kinase activity of insulin receptor isolated from rat adipocytes rendered insulin-resistant by catecholamine treatment in vitro. Biochem J 234: 59–66.
Harman D. 1981. The aging process. Proc Natl Acad Sci USA 78: 7124–7128.
Harr SD, Simonian NA, Hyman BT. 1995. Functional alterations in Alzheimer's disease: Decreased glucose transporter 3 immunoreactivity in the perforant pathway terminal zone. J Neuropathol Exp Neurol 54: 38–41.
Hart GW. 1997. Dynamic O-linked glycosylation of nuclear and cytoskeletal proteins. Annu Rev Biochem 66: 315–335.
Hartmann T. 1999. Intracellular biology of Alzheimer's disease amyloid beta peptides. Eur Arch Psychiatry Clin Neurosci 249: 291–298.
Hartmann T, Bieger SC, Brüh lB, Tienari PJ, Ida N, et al. 1997. Distinct sites of intracellular production for Alzheimer's disease Aβ 40/42 amyloid peptides. Nat Med 3: 1016–1020.
Hashiguchi M, Saito T, Hisanaga S, Hashiguchi T. 2002. Truncation of CDK5 activator p35 induces intensive phosphorylation of Ser202/Thr205 of human tau. J Biol Chem 277: 44525–44530.
Hassler R. 1938. Zur Pathologie der Paralysis agitans und des postenzephatischen Parkinsonismus. Z Psychiat Neurol 48: 387–476.
Hauger RL, Thrivikraman KV, Plotsky PM. 1994. Age-related alterations of hypothalamic-pituitary-adrenal axis function in male Fischer 344 rats. Endocrinology 134: 1528–1536.
Hawkins RA, Williamson DH, Krebs HA. 1971. Ketone-body utilization by adult and suckling rat brain in vivo. Biochem J 122: 13–18.
Hayes BK, Hart GW. 1998. Protein O-GlycNAcylation: Potential mechanisms for the regulation of protein function. Adv Exp Med Biol 435: 85–94.
Haute Van den C, Spittaels K, Van Dorpe J, Lasrado R, Vandezande K, et al. 2000. Coexpression of human cdk5 and its activator p35 with human protein tau in neurons in brain of triple transgenic mice. Neurobiol Dis 8: 32–44.
Heidenreich KA, Zahniser NR, Berhanu P, Brandenburg D, Olefsky JM. 1983. Structural differences between insulin receptors in the brain and peripheral target tissues. J Biol Chem 258: 8527–8530.
Held GA, Solina DH, Keane DT, Haag WJ, Horn PM, et al. 1990. Experimental study of critical mass-fluctuations in an evolving sandpile. Phys Rev Lett 69: 1120–1123.
Henneberg N, Hoyer S. 1994. Short-term or long-term intracerebroventricular (i.c.v.) infusion of insulin exhibits a discrete anabolic effect on cerebral energy metabolism in the rat. Neurosci Lett 175: 153–156.
Henneberg N, Hoyer S. 1995. Desensitiziation of the neuronal insulin receptor: A new approach in the etiopathogenesis of late-onset sporadic dementia of the Alzheimer type (SDAT)? Arch Gerontol Geriatr 21: 63–74.
Herholz K, Salmon E, Perani D, Baron DJ, Holthoff V, et al. 2002. Discrimination between Alzheimer dementia and controls by automated analysis of multicenter FDG PET. NeuroImage 17: 302–316.
Herrera A, Tomás-Camardiel M, Venero JL, Cano J, Machado A. 2005. Inflammatory process as a determinant factor for the degeneration of substantia nigra dopaminergic neurons. J Neural Transm 112: 111–120.
Hertz MM, Paulson OB, Barry DI, Christiansen JS, Svendsen PA. 1981. Insulin increases glucose transfer across the blood-brain barrier. J Clin Invest 67: 597–604.
Hess B. 1983. Non-equlibrium dynamics of biochemical processes. Hoppe-Seylers Z Physiol Chem 364: 1–20.
Hess B. 1990. Order and chaos in chemistry and biology. Fresenius Anal Chem 337: 459–468.
Hill JM, Lesniak MA, Pert CB, Roth J. 1986. Autoradiographic localization of insulin receptors in rat brain: Promince in olfactory and limbic areas. Neuroscience 17: 1127–1138.
Hirsch E, Graybiel AM, Agid YA. 1988. Melanized dopaminergic neurons are differentially susceptible to degeneration in Parkinson's disease. Nature 334: 345–348.
Hirschberg CB, Snider MD. 1987. Topography of glycosylation in the rough endoplasmic reticulum and Golgi apparatus. Ann Rev Biochem 56: 63–87.
Holness MJ, Langdown M, Sugden MC. 2000. Early-life programming of susceptibility to dysregulation of glucose metabolism and the development of type 2 diabetes mellitus. Biochem J 349: 657–665.
Holsinger RMD, McLean CA, Beyreuther K, Masters CL, Evin G. 2002. Increased expression of the amyloid precursor β-secretase in Alzheimer's disease. Ann Neurol 51: 783–786.
Hong MF, Lee VMY. 1997. Insulin and insulin-like growth factor-1 regulate tau phosyphorylation in cultured human neurons. J Biol Chem 272: 19547–19553.
Hoogendijk WJG, Feenstra MGP, Botterblom MHA, Gilhuis J, Sommer IEC, et al. 1999. Increased activity of surviving locus ceruleus neurons in Alzheimer's disease. Ann Neurol 45: 82–89.
Hotamisligil GS, Murray DL, Choy LN, Spiegelmann BM. 1994. Tumor necrosis factor α inhibits signalling from the insulin receptor. Proc Natl Acad Sci USA 91: 4854–4858.
Hotamisligil GS, Peraldi P, Budavari A, Ellis R, White MF, et al. 1996. IRS-1-mediated inhibition of insulin receptor tyrosine kinase activity in TNF-α- and obesity-induced insulin resistance. Science 271: 665–668.
Hoyer A, Bardenheuer JH, Martin E, Plaschke K. 2005. Amyloid precursor protein (APP) and its derivatives change after cellular energy depletion. An in vitro study. J Neural Transm 112: 239–253.
Hoyer S. 1970. Der Aminosäurenstoffwechsel des normalen menschlichen Gehirns. Klin Wschr 48: 1239–1243.
Hoyer S. 1985. The effect of age on glucose and energy metabolism in brain cortex of rats. Arch Gerontol Geriatr 4: 193–203.
Hoyer S. 1986. Senile dementia and Alzheimer's disease: Brain blood flow and metabolism. Prog Neuropsychopharmacol Biol Psychiatry 10: 447–478.
Hoyer S. 1988. Glucose and related brain metabolism in dementia of Alzheimer type and its morphological significance. Age 11: 158–166.
Hoyer S. 1992. Oxidative energy metabolism in Alzheimer brain. Studies in early-onset and late onset cases. Mol Chem Neuropathol 16: 207–224.
Hoyer S. 1995. Age-related changes in cerebral oxidative metabolism. Implications for drug therapy. Drugs Aging 6: 210–218.
Hoyer S. 1996. Oxidative metabolism deficiencies in brains of patients with Alzheimer's disease. Acta Neurol Scand Suppl 165: 18–24.
Hoyer S. 1998. Is sporadic Alzheimer disease the brain type of non-insulin dependent diabetes mellitus? A challenging hypothesis. J Neural Transm 105: 415–422.
Hoyer S. 2000a. The aging brain. Changes in the neuronal insulin/insulin receptor signal transduction cascade trigger late-onset sporadic Alzheimer disease (SAD). A mini-review. J Neural Transm 109: 991–1002.
Hoyer S. 2000b. Brain glucose and energy metabolism abnormalities in sporadic Alzheimer disease. Causes and consequences: An update. Exp Gerontol 35: 1363–1372.
Hoyer S. 2002. The brain insulin signal transduction system and sporadic (type II) Alzheimer disease: An update. J Neural Transm 109: 341–360.
Hoyer S. 2004a. Causes and consequences of disturbances of cerebral glucose metabolism in sporadic Alzheimer disease: Therapeutic implications. Adv Exp Med Biol 541: 135–152.
Hoyer S. 2004b. Glucose metabolism and insulin receptor signal transduction in Alzheimer disease. Eur J Pharmacol 490: 115–125.
Hoyer S, Betz K. 1988. Abnormalities in glucose and energy metabolism are more severe in the hippocampus than in the cerebral cortex in postischemic recovery in aged rats. Neurosci Lett 94: 167–172.
Hoyer S, Krier C. 1986. Ischemia and the aging brain. Studies on glucose and energy metabolism in rat cerebral cortex. Neurobiol Aging 7: 23–29.
Hoyer S, Lannert H, Latteier E, Meisel T. 2004. Relationship between cerebral energy metabolism in parietotemporal cortex and hippocampus and mental activity during aging in rats. J Neural Transm 111: 575–589.
Hoyer S, Nitsch R. 1989. Cerebral excess release of neurotransmitter amino acids subsequent to reduced cerebral glucose metabolism in early-onset dementia of Alzheimer type. J Neural Transm 75: 227–232.
Hoyer S, Nitsch R, Oesterreich K. 1990. Ammonia is endogenously generated in the brain in the presence of presumed and verified dementia of Alzheimer type. Neurosci Lett 117: 358–362.
Hoyer S, Nitsch R, Oesterreich K. 1991. Predominant abnormality in cerebral glucose utilization in late-onset dementia of the Alzheimer-type: A cross-sectional comparison against advanced late-onset dementia and incipient early-onset cases. J Neural Transm (PD-Sect) 3: 1–14.
Hoyer S, Oesterreich K, Wagner O. 1988. Glucose metabolism as the site of the primary abnormality in early-onset dementia of Alzheimer type. J Neurol 235: 143–148.
Hoyer S, Plaschke K. 2004. Brain damage and repair. From Molecular Research to Clinical Therapy. Herdegen T, Dilgado Garccia J, editors. Dordrecht, Boston, London: Kluwer; pp. 1–22.
Hoyer S, Prem L, Sorbi S, Amaducci L. 1993. Stimulation of glycolytic key enzymes in cerebral cortex by insulin. Neuroreport 4: 991–993.
Hughes K, Nikolakaki E, Plyte SE, Totty NF, Woodgett JR. 1993. Modulation of the glycogen synthase kinase-3 family by tyrosine phosphorylation. EMBO J 12: 803–808.
Hung HC, Tsai MJ, Wu HC, Lee EHY. 2000. Age-dependent increase in C7–1 gene expression in frontal rat cortex. Mol Brain Res 75: 330–336.
Hyman BT, van Hoesen GW, Damasio AR, Barnes CL. 1984. Alzheimer's disease: Cell-specific pathology isolates the hippocampal formation. Science 225: 1168–1170.
Hyman BT, van Hoesen GW, Kromer LJ, Damasio AR. 1986. Perforant pathway changes and the memory impairment of Alzheimer's disease. Ann Neurol 20: 472–481.
Ida Y, Tanaka M, Kohno Y, Nakagawa R, Iiomori K, et al. 1982. Effect of age and stress on regional noradrenaline metabolism in the rat brain. Neurobiol Aging 3: 233–236.
Iijima K, Ando K, Takeda S, Satoh Y, Seki T, et al. 2000. Neuron-specific phosphorylation of Alzheimer's beta-amyloid precursor protein by cyclindependent kinase 5. J Neurochem 75: 1085–1091.
Imahori K, Uchida T. 1997. Physiology and pathology of tau protein kinases in relation to Alzheimer's disease. J Biochem 121: 179–188.
Imai Y, Soda M, Takahashi R. 2000. Parkin suppresses unfolded protein stress-induced cell death through its E3 ubiquitation-protein ligase activity. J Biol Chem 275: 35661–35664.
Inagaki N, Gonor T, Clement JP, Wang CZ, Aquilar-Bryan L, et al. 1996. A family of sulfonylurea receptors determines the pharmacological properties of ATP-sensitive K+ channels. Neuron 16: 1101–1107.
Ishiguro K, Shiratsuchi A, Sato S, Omori A, Arioka M, et al. 1993. Glycogen synthase kinase 3-beta is identical to tau protein kinase I generating several epitopes of paired helical filaments. FEBS Lett 325: 167–172.
Ishiguro K, Takamatsu M, Tomizawa K, Omori A, Takahashi M, et al. 1992. Tau protein kinase I converts normal tau protein into A68-like component of paired helical filaments. J Biol Chem 267: 10897–10901.
Iwata N, Tsubuki S, Takaki Y, Shirotani K, Lu B, et al. 2001. Metabolic regulation of brain Aβ by neprilysin. Science 292: 1550–1552.
Iwata N, Tsubuki S, Takaki Y, Watanabe K, Sekiguchi M, et al. 2000. Identification of the major Aβ 1–42-degrading catabolic pathway in brain parenchyma: Suppression leads to biochemical and pathological deposition. Nat Med 6: 143–150.
Jellinck PH, Pavlides C, Sakai RR, McEwen BS. 1999. 11β-hydroxysteroid dehydrogenase functions reversibly as an oxidoreductase in the rat hippocampus in vivo. J Steroid Biochem Mol Biol 71: 139–144.
Jellinger K. 1987. Movement Disorders, Vol. 2. Marsden CD, Fahn S, editors. London: Butterworth; pp. 124–165.
Jellinger K, Danielczyk W. 1968. Striato-nigrale degeneration. Acta Neuropathol 10: 242–257.
Jenner P, 1998. Oxidative mechanisms in nigral cell death in Parkinson's disease. Mov Disord 13 (Suppl.): 24–34.
Jiang CH, Tsien JZ, Schultz PG, Hu Y. 2001. The effects of aging on gene expression in the hypothalamus and cortex of mice. Proc Natl Acad Sci USA 98: 1930–1934.
Johnson SA, Pasinetti GM, May PC, Ponte PA, Cordell B, et al. 1988. Selective reduction of mRNA for the beta-amyloid precursor protein that lacks a Kunitz-type protease inhibitor motif in cortex from Alzheimer brains. Exp Neurol 102: 264–268.
Joseph J, Shukitt-Hale B, Denisova NA, Martin A, Perry G, et al. 2001. Copernicus revisited: Amyloid beta in Alzheimer's disease. Neurobiol Aging 22: 131–146.
Kadekaro M, Crane AM, Sokoloff L. 1985. Differential effects of electrical stimulation of sciatic nerve on metabolic activity in spinal cord and dorsal root ganglion in the rat. Proc Natl Acad Sci USA 82: 6010–6013.
Kahn CR. 1985. The molecular mechanism of insulin action. Ann Rev Med 36: 429–451.
Kaufman RJ. 1999. Stress signalling from the lumen of the endoplasmic reticulum: Coordination of gene transcriptional and translational controls. Genes Dev 13: 1211–1233.
Kauppinen RA, Nicholls DG. 1986. Failure to maintain glycolysis in anoxic nerve terminals. J Neurochem 47: 1864–1869.
Keller JN, Pang Z, Geddes JW, Begley JG, Germeyer A, et al. 1997. Impairment of glucose and glutamate transport and induction of mitochondrial oxidative stress and dysfunction in synaptosomes by amyloid β-peptide: Role of the lipid peroxidation product 4-hydroxynonenal. J Neurochem 69: 273–284.
Kelly WG, Dahmus ME, Hart GW. 1993. RNA polymerase II is a glycoprotein: Modification of the COOH-terminal domain by O-GlcNAc. J Biol Chem 268: 10416–10424.
Kienlen-Campard P, Miolet S, Tasiaux B, Octave JN. 2002. Intracellular amyloid-β 1–42, but not extracellular soluble amyloid-β peptides, induces neuronal apoptosis. J Biol Chem 277: 15666–15670.
Kim SJ, Han Y. 2005. Insulin inhibits AMPA-induced neuronal damage via stimulation of protein kinase B (Akt). J Neural Transm 112: 179–191.
Kirschenbaum F, Hsu SC, Cordell B, McCarthy JV. 2001a. Substitution of a glycogen synthase kinase-3 phosphorylation site in presenilin 1 separates presenilin function from β-catenin signalling. J Biol Chem 276: 7366–7375.
Kirschenbaum F, Hsu SC, Cordell B, McCarthy JV. 2001b. Glycogen synthase kinase-3β regulates presenilin 1 C-terminal fragment levels. J Biol Chem 276: 30701–30707.
Klein J. 2000. Membrane breakdown in acute and chronic neurodegeneration: Focus on choline-containing phospholipids. J Neural Transm 107: 1027–1063.
Klein J, Fasshauer M, Ito M, Lowell BB, Benito M, et al. 1999. β3-Adrenergic stimulation differentially inhibits insulin signalling and decreases insulin-induced glucose uptake in brown adipocytes. J Biol Chem 274: 34795–34802.
Kliegel M, Moor C, Rott C. 2004. Cognitive status and development in the oldest old: A longitudinal analysis from the Heidelberg Centenarian Study. Arch Gerontol Geriatr 39: 143–156.
Kometiani ZP, Tsakadze LG, Jariashvili TY. 1984. Functional significance of the effects of neurotransmitters in the Na+, K+-ATPase system. J Neurochem 42: 1246–1250.
Kozutsumi Y, Segal M, Normington K, Gething MJ, Sambrook J. 1988. The presence of malfolded proteins in the endoplasmic reticulum signals the induction of glucose regulated proteins. Nature 332: 462–464.
Kreutzberg W. 1996. Microglia: A sensor for pathological events in the CNS. Trends Neurosci 19: 312–318.
Kuo WL, Montag AG, Rosner MR. 1993. Insulin-degrading enzyme is differentially expressed and developmentally regulated in various rat tissues. Endocrinology 132: 604–611.
Kurochkin IV, Goto S. 1994. Alzheimer's beta-amyloid peptide specifically interacts with and is degraded by insulin degrading enzyme. FEBS Lett 345: 33–37.
Kusakawa G, Saito T, Onuki R, Ishiguro K, Kishimoto T, et al. 2000. Calpain-dependent proteolytic cleavage of the p35 cyclindependent kinase 5 activator to p25. J Biol Chem 275: 17166–17172.
Kyriakis JM, Hausman RE, Peterson SW. 1987. Insulin stimulates choline acetyltransferase activity in cultured embryonic chicken retina neurons. Proc Natl Acad Sci USA 84: 7463–7467.
Lai JCK, Cooper AJL. 1991. Neurotoxicity of ammonia and fatty acids: Differential inhibition of mitochondrial dehydrogenases by ammonia and fatty acids coenzyme A derivatives. Neurochem Res 16: 795–803.
Lannert H, Gorgas K, Meiβner I, Wieland FT, Jeckel D. 1998. Functional organization of the Golgi apparatus in glycosphingolipid biosynthesis. J Biol Chem 273: 2939–2946.
Lannert H, Hoyer S. 1998. Intracerebroventricular administration of streptozotocin causes long-term diminutions in learning and memory abilities and in cerebral energy metabolism in adult rats. Behav Neurosci 112: 1199–1208.
Lannfelt L, Basun H, Wahlund LO, Rowe BA, Wagner SL. 1995. Decreased α-secretase-cleaved amyloid precursor protein as a diagnostic marker for Alzheimer's disease. Nat Med 1: 829–832.
Leanza G. 1998. Chronic elevation of amyloid precursor protein expression in the neocortex and hippocampus of rats with selective cholinergic lesions. Neurosci Lett 257: 53–56.
Lee J, Stock J. 1993. Protein phosphatase 2A catalytic subunit is methylesterified at its carboxyl terminus by a novel methyltransferase. J Biol Chem 268: 19192–19195.
Lee K, Dixon AK, Rowe ICM, Ashford MJK, Richardson PJ. 1996. The high-affinity sulfonylurea receptors regulates KATP channels in nerve terminal of the rat motor cortex. J Neurochem 66: 2562–2571.
Lee MS, Kwon YT, Li M, Peng J, Friedlander RM, et al. 2000. Neurotoxicity induces cleavage of p35 to p25 by calpain. Nature 405: 360–364.
Leibovitz BE, Siegel BV. 1980. Aspects of free radical reactions in biological systems: aging. J Gerontol 35: 45–56.
Leloup C, Arluison M, Lepetit N, Cartier N, Marfaing-Jallat P, et al. 1994. Glucose transporter 2 (GLUT2): Expression in specific brain nuclei. Brain Res 638: 221–226.
Lesort M, Jope RS, Johnson GVW. 1999. Insulin transiently increases tau phosphorylation: Involvement of glycogen synthase kinase-3β and Fyn tyrosine kinase. J Neurochem 72: 576–584.
Levin BE, Dunn-Meynell AA. 1997. In vivo and in vitro regulation of (3H) glyburide binding to brain sulfonylurea receptors in obesity-prone and resistant rats by glucose. Brain Res 776: 146–153.
Levine RL, Oliver CN, Fulks RM, Stadtman ER. 1981. Turnover of bacterial glutamine synthetase: Oxidative inactivation precedes proteolysis. Proc Natl Acad Sci USA 78: 2120–2124.
Lewis LD, Ljunggren B, Ratcheson RA, Siesjö BK. 1974. Cerebral energy state in insulin-induced hypoglycaemia, related to blood glucose and to EEG. J Neurochem 23: 673–679.
Li BS, Sun MK, Zhang L, Takahashi S, Ma W, et al. 2001. Regulation of NMDA receptors by cyclin-dependent kinase-5. Proc Natl Acad Sci USA 98: 12742–12747.
Li C, Booze RM, Hersh LB. 1995a. Tissue-specific expression of rat neutral endopeptidase (neprilysin) mRNAs. J Biol Chem 270: 5723–5728.
Li JJ, Surini M, Catsicas S, Kawashima E, Bouras C. 1995b. Age-dependent accumulation of advanced glycation end products in human neurons. Neurobiol Aging 16: 69–76.
Li M, Wang X, Meintzer M, Laessig T, Birnbaum MJ, et al. 2000. Cyclic AMP promotes neuronal survival by phosphorylation of glycogen synthase kinase 3β. Mol Cell Biol 20: 9356–9363.
Lieb K, Fiebich BL, Schaller H, Berger M, Bauer J. 1996. Interleukin-1 beta and tumor necrosis factor-alpha induce expression of alpha 1-antichymotrypsin in human astrocytoma cells by activation of nuclear factor-kappa B. J Neurochem 67: 2039–2044.
Lin T, Le Blanc CJ, Deacon TW, Isascon O. 1998. Chronic cognitive deficits and amyloid precursor protein elevation after selective immunnotoxin lesions of the basal forebrain cholinergic system. Neuroreport 9: 547–552.
Lippa AS, Critchett DJ, Ehlert F, Yamamura HI, Enna SJ, et al. 1981. Age-related alterations in neurotransmitter receptors: An electrophysiological and biochemical analysis. Neurobiol Aging 2: 3–8.
Lipton SA. 1997. Janus faces of NFKB activity: Neurodestruction versus neuroprotection. Nat Med 3: 20–22.
Liu F, Iqbal K, Grundke-Iqbal I, Hart GW, Gong CX. 2004. O-GlycNacylation regulates phosphorylation of tau: A unique mechanism involved in Alzheimer's disease. Proc Natl Acad Sci USA 101: 19804–19809.
Lorens SA, Hata N, Handa RJ, van de Kar LD, Guschwan M, et al. 1990. Neurochemical, endocrine and immunological responses to stress in young and old Fischer 344 male rats. Neurobiol Aging 11: 139–150.
Loring JF, Wen X, Lee JM, Seilhamer J, Somogyi R. 2001. A gene expression profile of Alzheimer's disease. DNA Cell Biol 20: 683–695.
Lovestone S, Reynolds CH. 1997. The phosphorylation of tau: A critical stage in neurodevelopment and neurodegenerative processes. Neuroscience 78: 309–324.
Lowe WL Jr, Boyd FT, Clarke DW, Raizada MK, Hart C, et al. 1986. Development of brain insulin receptors: Structural and functional studies of insulin receptors from whole brain and primary cell cultures. Endocrinology 119: 25–35.
Lue L, Walker D, Rogers J. 2001. Modeling microglial activation in Alzheimer's disease with human postmortem microglial cultures. Neurobiol Aging 22: 945–956.
Lupien S, Lecors A, Lussier I, Schwartz G, Nair N, et al. 1994. Basal cortisol levels and cognitive deficits in human aging. J Neurosci 14: 2893–2903.
Maes M, De Vos N, Wauters A, Demedts P, Maurits VW, et al. 1999. Inflammatory markers in younger vs elderly normal volunteers and in patients with Alzheimer's disease. J Psychiatry Res 33: 397–405.
Maher F, Simpson IA, Vannucci SJ. 1993. Alterations in brain glucose transporter proteins GLUT1 and GLUT3, in streptozotocin diabetic rats. Adv Exp Med Biol 331: 9–12.
Mandelkow EM, Drewes G, Biernet J, Gustke N, van Lint J, et al. 1992. Glycogen synthase kinase-3 and the Alzheimer-like state of microtubule-associated protein tau. FEBS Lett 314: 215–221.
Marsden CD. 1990. Parkinson's disease. Lancet 335: 948–952.
Martinez M, Fernandez E, Frank A, Guaza C, de la Fuente M, et al. 1999. Increased cerebrospinal fluid cAMP levels in Alzheimer's disease. Brain Res 846: 265–267.
Mastrogiacomo F, Bergeron C, Kish SJ. 1993. Brain α-ketoglutarate dehydrogenase complex activity in Alzheimer's disease. J Neurochem 61: 2007–2014.
Mauch DH, Nägler J, Schumacher S, Göritz EC, Otto A, et al. 2001. CNS synaptogenesis promoted by glia-derived cholesterol. Science 294: 1354–1357.
McCusker SM, Curran MD, Dynan KB, McCullagh CD, Urquhart DD, et al. 2001. Association between polymorphism in regulatory region of gene encoding tumour necrosis factor α and risk of Alzheimer's disease and vascular dementia: A case-control study. Lancet 337: 436–439.
McDermott JR, Gibson AM. 1997. Degradation of Alzheimer's beta-amyloid protein by human and rat brain peptidases: Involvement of insulin-degrading enzyme. Neurochem Res 22: 49–56.
McMillan PJ, Leverenz JB, Dorsa DM. 2000. Specific downregulation of presenilin 2 gene expression is prominent during early stages of sporadic late-onset Alzheimer's disease. Brain Res Mol Brain Res 78: 138–145.
McMillan PJ, Leverenz JB, Poorkaj P, Schellenberg GC, Dorsa DM. 1996. Neuronal expression of STM2 mNRA in human brain is reduced in Alzheimer's disease. J Histochem Cytochem 44: 1215–1222.
Merkel P, Khoury N, Bertolotto C, Perfetti R. 2003. Insulin and glucose regulate the expression of the DNA repair enzyme XPD. Mol Cell Endocrinol 201: 75–85.
Michikawa M, Yanagisawa K. 1999. Inhibition of cholesterol production but not of nonsterol isoprenoid products induces neuronal cell death. J Neurochem 72: 2278–2285.
Mielke R, Herholz K, Grond M, Heiss WD. 1994. Clinical deterioration in probable Alzheimer's disease correlates with progressive metabolic impairment of association areas. Dementia 5: 36–41.
Mielke R, Herholz K, Grond M, Kessler J, Heiss WD. 1992. Differences of regional cerebral glucose metabolism between presenile and senile dementia of Alzheimer type. Neurobiol Aging 13: 93–98.
Miller BC, Eckman EA, Sambamurti K, Dobbs N, Chon KM, et al. 2003. Amyloid-β peptide levels in brain are inversely correlated with insulysin activity levels in vivo. Proc Natl Acad Sci USA 100: 6221–6226.
Mindham RH, Ahmed SW, Clough CG. 1992. A controlled study of dementia in Parkinson's disease. J Neurol Neurosurg Psychiatry 45: 969–974.
Minoshima S, Giordani B, Berent S, Frey KA, Foster NL, et al. 1997. Metabolic reduction in the posterior cingulate cortex in very early Alzheimer's disease. Ann Neurol 42: 85–94.
Mirollo RE, Strogatz SH. 1990. Synchronization of pulse-coupled biological oscillators. SIAM J Appl Math 50: 1645–1649.
Moll G, Gsell W, Wichart I, Jellinger K, Riederer P. 1990. Alzheimer's Disease: Epidemiology, Neuropathology, Neurochemistry, and Clinics. Maurer K, Riederer P, Beckmann H, editors. New York: Springer Wien; pp. 235–243.
Monnier VM, Cerami A. 1991. Nonenzymatic browning in vivo: Possible process for aging of long-lived proteins. Science 211: 491–493.
Moss AM, Unger JW, Moxley RT, Livingston JN. 1990. Location of phosphotyrosine-containing proteins by immunocytochemistry in the rat forebrain corresponds to the distribution of insulin receptor. Proc Natl Acad Sci USA 87: 4453–4457.
Mourre C, Ben Ari Y, Bernardi H, Fosset M, Lazdunski M. 1989. Antidiabetic sulfonylureas: Localization of binding sites in the brain and effects on the hyperpolarization induced by anoxia in hippocampal slices. Brain Res 486: 159–164.
Mukherjee A, Song E, Kihiko-Ehmann M, Goodman JP Jr, St Pyrek J, et al. 2000. Insulysin hydrolyzes amyloid β peptide to products that are neither neurotoxic nor deposit on amyloid plaques. J Neurosci 20: 8745–8749.
Mulder M, Ravid R, Swaab DF, de Kloet ER, Haasdijk ED, et al. 1998. Reduced levels of cholesterol phospholipids, and fatty acids in cerebrospinal fluid of Alzheimer disease patients are not related to apolipoprotein E4. Alzheimer Dis Assoc Disord 12: 198–203.
Mullamy P, Conolly S, Lynch MA. 1996. Ageing is associated with changes in glutamate release, protein tyrosine kinase and Ca2+/ calmodulin-dependent protein kinase II in rat hippocampus. Eur J Pharmacol 309: 311–315.
Münch G, Apelt J, Kientsch-Engel R, Stahl P, Lüth H, et al. 2003. Advanced glycation endproducts and pro-inflammatory cytokines in transgenic Tg 2576 mice with amyloid plaque pathology. J Neurochem 86: 283–289.
Münch G, Schinzel R, Loske C, Wong A, Durany N, et al. 1998. Alzheimer's disease-synergistic effects of glucose deficit, oxidative stress and advanced glycation endproducts. J Neural Transm 105: 439–461.
Munro S, Pelham HR. 1986. An Hsp 70-like protein in the ER: identity with the 78 kd glucose-regulated protein and immunoglobulin heavy chain binding protein. Cell 46: 291–300.
Nath R, Davis M, Probert AW, Kupina NC, Ren X, et al. 2000. Processing of cdk5 activator p35 to its truncated form (p25) by calpain in acutely injured neuronal cells. Biochem Biophys Res Commun 274: 16–21.
Newsholm EA, Start C. 1973. Regulation in metabolism. Wiley; Chichester: pp. 88–145.
Nichols NR. 1999. Glial responses to steroids as markers of brain aging. J Neurobiol 40: 585–601.
Nikolic M, Dudek H, Kwon YT, Ramos YF, Tsai LH. 1996. The cdk5/ p35 kinase is essential for neurite outgrowth during neuronal differentiation. Genes Dev 10: 816–825.
Nitsch R, Hoyer S. 1991. Local action of the diabetogenic drug, streptozotocin, on glucose and energy metabolism in rat brain cortex. Neurosci Lett 128: 199–202.
Nitsch RM, Blusztajn JK, Pittas AG, Slack BE, Grodwon JH, et al. 1992b. Evidence for a membrane defect in Alzheimer's disease brain. Proc Natl Acad Sci USA 89: 1671–1675.
Nitsch RM, Slack BE, Wurtman RJ, Growdon J. 1992a. Release of Alzheimer amyloid precursor derivatives stimulated by activation of muscarinic acetylcholine receptors. Science 258: 304–307.
Noble W, Olm V, Takata K, Casey E, Mary O, et al. 2003. Cdk5 is a key factor in tau aggregation and tangle formation in vivo. Neuron 38: 555–565.
Nohl H, Krämer R. 1980. Molecular basis of age-dependent changes in the activity of adenine nucleotide translocase. Mech Ageing Dev 14: 137–144.
Norberg K, Siesjö BK. 1976. Oxidative metabolism of the cerebral cortex of the rat in insulin-induced hypoglycaemia. J Neurochem 26: 345–352.
Nordstedt C, Candy SE, Alafuzoff I, Caporaso GL, Iverfeldt K, et al. 1991. Alzheimer beta/A4 amyloid precursor protein in human brain: Aging-associated increases in holoprotein and in a proteolytic fragment. Proc Natl Acad Sci USA 88: 8910–8914.
O'Brien JT, Ames D, Schweitzer I, Mastwyk M, Colman P. 1996. Enhanced adrenal sensitivity to adrenocorticotrophic hormone (ACTH) is evident of HPA axis hyperactivity in Alzheimer's disease. Psychol Med 26: 7–14.
Ohtsuka K, Suzuki T. 2000. Roles of molecule chaperones in the nervous system. Brain Res Bull 53: 141–146.
Ott A, Breteler MMB, van Harskamp F, Claus JJ, Cammen van der TJM, et al. 1995. Prevalence of Alzheimer's disease and vascular dementia: Association with education. The Rotterdam study. Br J Med 310: 970–973.
Owen OE, Morgan AP, Kemp HG, Sullivan JM, Herrera MG, et al. 1967. Brain metabolism during fasting. J Clin Invest 46: 1589–1597.
Oxenkrug GF, Pomara N, McIntyre IM, Branconnier RJ, Stanley M, et al. 1983. Aging and cortisol resistance to suppression by dexamethasone: A positive correlation. Psychiatry Res 10: 125–130.
Palmert MR, Golde TE, Cohen ML, Kovacs DM, Tanzi RE, et al. 1988. Amyloid protein precursor messenger RNAs: Differential expression in Alzheimer's disease. Science 241: 1080–1084.
Pardridge WM, Boado RJ, Farrell CR. 1990. Brain-type glucose transporter (GLUT-1) is selectively localized to the blood-brain barrier. Studies with quantitative Western blotting and in situ hybridization. J Biol Chem 265: 18035–18040.
Pardridge WM, Eisenberg J, Yang J. 1985. Human blood-brain barrier insulin receptor. J Neurochem 44: 1771–1778.
Parhad IM, Scott JN, Cellars LA, Bains JS, Krekoski CA, et al. 1995. Axonal atrophy in aging is associated with a decline in neurofilament gene expression. J Neurosci Res 41: 355–366.
Park CR. 2001. Cognitive effects of insulin in the central nervous system. Neurosci Biohav Rev 25: 311–323.
Parker WD, Parks J, Filley CM, Kleinschmidt-De Masters BK. 1994. Electron transport chain defects in Alzheimer's disease brain. Neurology 44: 1090–1096.
Parkinson J. 1817. Essay on the Shaking Palsy. London: Whittingham & Bowland.
Paschen W, Frandsen A. 2001. Endoplasmic reticulum dysfunction-a common denominator for cell injury in acute and degenerative diseases of the brain? J Neurochem 79: 719–725.
Pascualy M, Petrie EC, Brodkin K, Peskind ER, Wilkinson W, et al. 2000. Hypothalamic pituitary adrenocortical and sympathetic nervous system responses to the cold pressure test in Alzheimer's disease. Biol Psychiatry 48: 247–254.
Payne J, Maher F, Simpson U, Mattice L, Davies P. 1997. Glucose transporter Glut 5 expression in microglial cells. Glia 21: 327–331.
Pearson RCA, Esiri MM, Hiorns RW, Wilcock GK, Powell TPS. 1985. Anatomical correlates of the distribution of the pathological changes in the neocortex in Alzheimer disease. Proc Natl Acad Sci USA 82: 4531–4534.
Peraldi Hotamisligil GS, Buurman WA, White MF, Spiegelman BM. 1996. Tumor necrosis factor (TNF)-α inhibits insulin signaling through stimulation of the p55TNF receptor and activation of sphingomyelinase. J Biol Chem 271: 13018–13022.
Perego C, Vetrugno CC, de Simoni MG, Algeri S. 1993. Aging prolongs the stress-induced release of noradrenaline in rat hippocampus. Neurosci Lett 157: 127–130.
Perez A, Morelli L, Cresto JC, Castano EM. 2000. Degradation of soluble amyloid β-peptides 1–40, 1–42, and the Dutch variant 1–40 Q by insulin degrading enzyme from Alzheimer disease and control brain. Neurochem Res 25: 247–255.
Perry EK, Perry RG, Tomlinson BE, Blessed G, Gibson PH. 1980. Coenzyme A-acetylating enzymes in Alzheimer's diseae: Possible cholinergic “compartment” of pyruvate dehydrogenase. Neurosci Lett 18: 105–110.
Peskind ER, Elrod R, Dobie DJ, Pascualy M, Petrie E, et al. 1998. Cerebrospinal fluid epinephrine in Alzheimer's disease and normal aging. Neuropsychopharmacology 19: 465–471.
Peskind ER, Wilkinson CW, Schellenberg EC, Raskind MA. 2001. Increased CSF cortisol in AD is a function of APOE genotype. Neurology 56: 1094–1098.
Peskind ER, Wingerson D, Murray S, Pascualy M, Dobie DJ, et al. 1995. Effects of Alzheimer's disease and normal aging on cerebrospinal fluid norepinephrine responses to yohimbine and clonidine. Arch Gen Psychiatry 52: 774–782.
Petanceska SS, Gandy S. 1999. The phosphatidylinositol 3-kinase inhibitor wortmannin alters the metabolism of the Alzheimer's amyloid precursor protein. J Neurochem 73: 2316–2320.
Pettegrew JW, Klunk WE, Kanal E, Panchalingam K, McClure RJ. 1995. Changes in brain membrane phospholipids and high-energy phosphate metabolism precede dementia. Neurobiol Aging 16: 973–975.
Phiel CJ, Wilson CA, Lee VMY, Klein PS. 2003. GSK-3α regulates production of Alzheimer's disease amyloid-β peptides. Nature 423: 435–439.
Pigino G, Paglini G, Ulloa L, Avila J, Caceres A. 1997. Analysis of the expression, distribution and function of cyclin dependent kinase 5 (cdk5) in developing cerebellar macroneurons. J Cell Sci 110 (Pt. 2): 257–270.
Pillon B, Dubois B, Lhermitte F, Agid Y. 1986. Heterogeneity of cognitive impairment in progressive supranuclear palsy Parkinson's disease, and Alzheimer's disease. Neurology 36: 1179–1185.
Planel E, Miyasaka I, Launey T, Chui DH, Tanermura K, et al. 2004. Alteration in glucose metabolism induce hypothermia leading to tau hyperphosphorylation through differential inhibition of kinase and phosphatase activities: implications for Alzheimer's disease. J Neurosci 24: 2401–2411.
Planel E, Yasutake K, Fujita SC, Ishiguro K. 2001. Inhibition of protein phosphatase 2A overrides tau protein kinase I/glycogen synthase kinase 3β and cyclin-dependent kinase 5 inhibition and results in tau hyperphosphorylation in the hippocampus of starved mice. J Biol Chem 276: 34298–34306.
Plata-Salaman CR. 1991. Insulin in the cerebrospinal fluid. Neurosci Biobehav Rev 15: 243–258.
Plee-Gautier E, Grimal H, Aggerbeck M, Barouki R, Forest C. 1998. Cytosolic aspartate aminotransferase gene is a member of the glucose-regulated protein gene family in adipocytes. Biochem J 329: 37–40.
Prigoine I. 1989. What is entropy? Naturwissenschaften 76: 1–8.
Procter AW, Palmer AM, Francis PT, Lowe SL, Neary D, et al. 1988. Evidence of glutamatergic denervation and possible abnormal metabolism in Alzheimer's disease. J Neurochem 50: 790–802.
Raizada ML, Shemer J, Judkins JH, Clarke DW, Masters BA, et al. 1988. Insulin receptors in the brain: Structural and physiological characterization. Neurochem Res 13: 297–303.
Ramakrishna S, Benjamin WB. 1998. Insulin action rapidly decreases multifunctional protein kinase activity in rat adipose tissue. J Biol Chem 263: 12677–12681.
Ramirez MJ, Ridley RM, Baker HF, Maclean CJ, Honer WG, et al. 2001. Chronic elevation of amyloid precursor protein in the neocortex or hippocampus of marmosets with selective cholinergic lesions. J Neural Transm 108: 809–826.
Rehncrona S, Hauge HN, Siesjö BK. 1989. Enhancement of iron-catalized free radical formation by acidosis in brain homogenates: Difference in effect by lactic acid and CO2. J Cereb Blood Flow Metab 9: 65–70.
Reid WG, Hely MA, Morris JGL, Broe GA, Adena M, et al. 1996. A longitudinal study of Parkinson's disease: Clinical and neuropathological correlates of dementia. J Clin Neurosci 3: 327–333.
Reul JMHM, Rothuizen J, Dekloet ER. 1991. Age-related changes in the dog hypothalamic-pituitary-adrenocortical system: Neuroendocrine activity and corticosteroid receptors. J Steroid Biochem Mol Biol 40: 63–69.
Reul JMHM, Tonnaer JADM, de Kloet ER. 1988. Neurotropic ACTH analogue promotes plasticity of type I corticosteroid receptors in brain of senescent rats. Neurobiol Aging 9: 253–260.
Reynolds CH, Utton MA, Gibb GM, Yates A, Anderton BH. 1997. Stress-activated protein kinase/c-jun N-terminal kinase phosphorylates tau-protein. J Neurochem 68: 1736–1744.
Riederer P, Sofic E, Rausch WD, Schmidt B, Reynolds GP, et al. 1989. Transition metals, ferritin, glutathione, and ascorbic acid in parkinsonian brains. J Neurochem 52: 515–520.
Rinaudo MT, Curto M, Bruno R, Marino C, Rossetti V, et al. 1987. Evidence of an insulin generated pyruvate dehydrogenase stimulating factor in rat brain plasma membranes. Ital J Biochem 19: 909–913.
Roberts EK Jr, Chih CP. 1995. Age-related alterations in energy metabolism contribute to the increased vulnerability of the aging brain to anoxic damage. Brain Res 678: 83–90.
Roberts EL Jr, Sick TJ. 1996. Aging impairs regulation of intracellular pH in rat hippocampal slices. Brain Res 735: 339–342.
Rocchi A, Pellegrini S, Siciliano G, Murri K. 2003. Causative and susceptibility genes for Alzheimer's disease: A review. Brain Res Bull 61: 1–24.
Roceri M, Hendriks W, Racagni G, Ellenbroek BA, Riva MA. 2002. Early maternal deprivation reduces the expression of BDNF and NMDA receptor subunits in rat hippocampus. Mol Psychiatry 7: 609–616.
Röder HM, Ingram VM. 1991. Two novel kinases phosphorylate tau and the KSP site of heavy neurofilament subunits in high stoichiometric ratios. J Neurosci 11: 3325–3342.
Roland BL, Li KXZ, Funder JW. 1995. Hybridization histochemical localization of 11β-hydroxysteroid dehydrogenase type 2 in rat brain. Endocrinology 136: 4697–4700.
Rossner S, Weberham U, Yu J, Kirazov L, Schliebs R, et al. 1997. In vivo regulation of amyloid precursor protein secretion in rat neocortex by cholinergic activity. Eur J Neurosci 9: 2125–2134.
Roth J. 1987. Subcellular organization of glycosylation in mammalian cells. Biochim Biophys Acta 906: 405–436.
Roth J, Taatjes DJ, Lucocq JM, Weinstein J, Paulson JC. 1985. Demonstration of an extensive trans-tubular network continuous with the Golgi apparatus stack that may function in glycosylation. Cell 43: 287–295.
Rothman JE. 1996. The protein machinery of vesicle budding and fusion. Protein Sci 5: 185–194.
Rothman JE, Orci L. 1992. Molecular dissection of the secretory pathway. Nature 355: 409–415.
Rothman JE, Wieland FT. 1996. Protein sorting by transport vesicles. Science 272: 227–234.
Ruderman NB, Ross PS, Berger M, Goodman MN. 1974. Regulation of glucose and ketone body metabolism in brain of unaesthetized rats. Biochem J 138: 1–10.
Rui L, Aguirre V, Kim JK, Shulman GI, Lee A, et al. 2001. Insulin/IGF-1 and TNF-α stimulate phosphorylation of IRS-1 at inhibitory Ser307 via distinct pathways. J Clin Invest 107: 181–189.
Rupprecht R, Holsboer F. 1999. Neuroactive steroids: Mechanism of action and neuropsychopharmacological perspectives. Trends Neurosci 22: 410–416.
Sacks W. 1957. Cerebral metabolism of isotopic glucose in normal human subjects. J Appl Physiol 10: 37–44.
Sakai RR, Lakshmi V, Monder C, McEwen BS. 1992. Immunocytochemical localization of 11 beta-hydroxysteroid dehydrogenase in hippocampus and other brain regions of the rat. J Neuroendocrinol 4: 101–106.
Salehi A, Swaab DF. 1999. Diminished neuroal metabolic activity in Alzheimer's diseae. J Neural Transm 106: 955–986.
Salehi M, Hodgkins MA, Merry BJ, Goyns MJ. 1996. Age-related changes in gene expression in the rat brain revealed by differential display. Experientia 52: 888–891.
Santos MS, Pereira EM, Carvaho AP. 1999. Stimulation of immunoreactive insulin release by glucose in rat brain synaptosomes. Neurochem Res 24: 33–36.
Sapolsky RM. 1999. Glucocorticoids, stress, and their adverse neurological effects: Relevance to aging. Exp Gerontol 34: 721–732.
Sapolsky RM, Krey LC, McEwen BS. 1983. The adrenocortical stress-response in the aged male rat: Impairment of recovery from stress. Exp Gerontol 18: 55–64.
Sapolsky RM, Krey LC, McEwen BS. 1986. The neuroendocrinology of stress and aging. The glucocorticoid cascade hypothesis. Endocrin Res 7: 284–300.
Sapolsky RM, Zola-Morgan S, Squire LR. 1991. Inhibition of glucocorticoid secretion by the hippocampal formation in the primate. J Neurosci 11: 3695–3704.
Sato A, Sato Y. 1995. Cholinergic neural regulation of regional cerebral blood flow. Alzheimer Dis Assoc Dis 9: 28–38.
Sawada M, Sester U, Calson JC. 1992. Superoxide radical formation and associated biochemical alterations in the plasma membrane of brain, heart, and liver during the lifetime of the rat. J Cell Biochem 58: 296–304.
Schechter R, Beju D, Gaffney T, Schaefer F, Whetsell L. 1996. Preproinsulin I and II mRNAs and insulin electron microscopic immuno-reaction are present within the fetal nervous system. Brain Res 736: 16–27.
Schechter R, Whitmire J, Holtzelaw L, George M, Devaskar SU. 1992. Developmental regulation of insulin in the mammalian central nervous system. Brain Res 582: 27–37.
Schipper HM. 1996. Astrocytes, brain aging and neurodegeneration. Neurobiol Aging 17: 467–480.
Schmidt R, Schmidt H, Curb JD, Masaki K, White LR, et al. 2002. Early inflammation and dementia: A 25-year follow-up of the Honolulu-asian aging study. Ann Neurol 52: 168–174.
Schwartz A, Lindenmayer GE, Allen JC. 1975. The sodium-potassium adenosine triphosphatase. Pharmacological, physiological and biochemical aspects. Pharmacol Rev 27: 3–134.
Seckl JR, Walker BR. 2001. Minireview: 11β-hydroxysteroid dehydrogenase type 1-a tissue-specific amplifier of glucocorticoid action. Endocrinology 142: 1371–1376.
Seksek O, Biwersi J, Verkman AS. 1995. Direct measurement of trans-Golgi pH on living cells and regulation by second messengers. J Biol Chem 270: 4967–4970.
Selkoe DJ. 1993. Physiological production of the β-amyloid protein and the mechanism of Alzheimer's disease. Trends Neurosci 16: 403–409.
Seubert P, Vigo-Pelfrey C, Esch F, Lee M, Dovey H, et al. 1992. Isolation and quantification of soluble Alzheimer's β-peptide from biological fluids. Nature 359: 325–327.
Sharpe JA, Rewcastle NB, Lloyd KG, Hornykiewicz O, Hill M, et al. 1973. Striatonigral degeneration: Response to levadopa therapy with pathological and neurochemical correlation. J Neural Sci 19: 275–286.
Shaw M, Cohen P, Alessi DR. 1997. Further evidence that the inhibition of glycogen synthase kinase-3β by IGF-1 is mediated by PDK1/PKB-induced phosphorylation of Ser-9 and not by dephosphorylation of Tyr-216. FEBS Lett 416: 307–311.
Shi J, Xiang Y, Simpkins JW. 1997. Hypoglycemia enhances the expression of mRNA encoding β-amylod precursor protein in rat primary cortical astroglial cells. Brain Res 772: 247–251.
Siesjö BK. 1978. Brain Energy Metabolism. Chichester; Wiley; pp. 1–28, 151–209.
Sims NR, Bowen DM, Allen SJ, Smith CCT, Neary D, et al. 1983a. Presynaptic cholinergic dysfunction in patients with dementia. J Neurochem 40: 503–509.
Sims NR, Bowen DM, Neary D, Davison AN. 1983b. Metabolic processes in Alzheimer's disease: Adenine nucleotide content and production of 14C02 from (U 14C) glucose in vivo in human neocortex. J Neurochem 41: 1329–1334.
Singh H, Usher S, Poulos A. 1989. Mitchondrial and peroxisomal beta-oxidation of stearic and lignoceric acids by rat brain. J Neurochem 53: 1711–1718.
Skovronsky DM, Doms RW, Lee VMY. 1998. Detection of a novel intraneuronal pool of insoluble amyloid β protein that accumulates with time in culture. J Cell Biol 141: 1031–1039.
Smith CD, Carney JM, Starke-Reed PE, Oliver CN, Stadtman ER, et al. 1991. Excess brain protein oxidation and enzyme dysfunction in normal aging and in Alzheimer disease. Proc Natl Acad Sci USA 88: 10540–10543.
Smith MA, Taneda S, Richey PL, Miyata S, Yan SD, et al. 1994. Advanced Maillard reaction end products are associated with Alzheimer disease pathology. Proc Natl Acad Sci USA 91: 5710–5714.
Sokoloff L. 1981. Localization of functional activity in the central nervous system by measurement of glucose utilization with radioactive deoxyglucose. J Cereb Blood Flow Metab 1: 7–36.
Solano DC, Sironi M, Bonfini C, Solarte SB, Govoni S, et al. 2000. Insulin regulates soluble amyloid precursor protein release via phosphatidyl inositol 3 kinase-dependent pathway. FASEB J 14: 1015–1022.
Sontag E, Hladik C, Montgomery L, Luangpirom A, Mudrak I, et al. 2004a. Downregulation of protein phosphatase 2A carboxyl methylation and methyltransferase may contribute to Alzheimer disease pathogenesis. J Neuropathol Exp Neurol 63: 1080–1091.
Sontag E, Luangpirom A, Hladik C, Mudrack I, Ogris E, et al. 2004b. Altered expression levels of the protein phosphatase 2 A ABαC enzyme are associated with Alzheimer disease pathology. J Neuropathol Exp Neurol 63: 287–301.
Sontag E, Nunbhakdi-Craig V, Bloom GS, Mumby MC. 1995. A novel pool of protein phosphatase 2A is associated with microtubules and is regulated during the cell cycle. J Cell Biol 128: 1131–1144.
Sorbi S, Bird ED, Blass JP. 1983. Decreased pyruvate dehydrogenase complex activity in Huntington and Alzheimer brain. Ann Neurol 13: 72–78.
Spanswick D, Smith MA, Mirshamsi S, Routh VH, Ashford MJL. 2000. Insulin activates ATP-sensitive K+ channels in hypothalamic neurons of lean, but not obese rats. Nat Neurosci 3: 757–758.
Stadtman ER. 1992. Protein oxidation and aging. Science 257: 1220–1224.
Stadtman ER, Berlett BS. 1991. Fenton chemistry. Amino acid oxidation. J Biol Chem 266: 17201–17211.
Stadtman ER, Oliver CN. 1991. Metal-catalized oxidation of proteins. Physiological consequences. J Biol Chem 266: 2005–2008.
Steen E, Terry BM, Rivera EJ, Cannon JL, Neely TR, et al. 2005. Impaired insulin and insulin-like growth factor expression and signaling mechanisms in Alzheimer's disease – is this type 3 diabetes? J Alzheimer Dis 7: 63–80.
Stover JF, Sakowitz OW, Schöning B, Rupprecht S, Kroppenstedt SN, et al. 2003. Norepinephrine infusion increases interleukin-6 in plasma and cerebrospinal fluid of brain-injured rats. Med Sci Monit 9: BR382–BR388.
Sun FF, Fleming WE, Taylor BM. 1993. Degradation of membrane phospholipids in the cultured human astroglial cell line UC-11MG during ATP depletion. Biochem Pharmacol 45: 1149–1155.
Sutherland C, Cohen P. 1994. The α-isoform of glycogen synthase kinase-3 from rabbit skeletal muscle is inactivated by p 70S6 kinase or MAP kinase-activated protein kinase-1 in vitro. FEBS Lett 338: 37–42.
Svennerholm L, Gottfries CG. 1994. Membrane lipids, selectively diminished in Alzheimer brains, suggest synapse loss as a primary event in early-onset form (type I) and demycelination in late-onset form (type II). J Neurochem 62: 1039–1047.
Swaab DF, Raadsheer FC, Endert EF, Hofman MA, Kamphorst WC, et al. 1994. Increases in cortisol levels in aging and Alzheimer's disease in postmortem cerebrospinal fluid. Neuroendocrinology 6: 681–687.
Sweeney G, Klip A. 1998. Regulation of the Na+/K+-ATPase by insulin: Why and how? Mol Cell Biochem 182: 121–133.
Takami K, Terai K, Matsuo A, Walker DG, McGeer PL. 1997. Expression of presenilin-1 and-2 mRNAs in rat and Alzheimer's disease brains. Brain Res 748: 122–130.
Takashima A, Murayama M, Murayama O, Kohno T, Honda T, et al. 1998. Presenilin 1 associates with glycogen kinase-3 β and its substrate tau. Proc Natl Acad Sci USA 95: 9637–9641.
Tarkowski E, Blennow K, Wallin A, Tarkowski A. 1999. Intracerebral production of tumor necrosis factor-α, a local neuroprotective agent, in Alzheimer disease and vascular dementia. J Clin Immun 19: 223–230.
Tham A, Nordberg A, Grissom FE, Carlsson-Skiwirut C, Viitanen M, et al. 1993. Insulin-like growth factors and insulin-like growth factor binding proteins in cerebrospinal fluid and serum of patients with dementia of the Alzheimer type. J Neural Transm (P-D Sect) 5: 165–176.
Tomizawa K, Ohta J, Matsushita M, Moriwaki A, Li ST, et al. 2002. Cdk5/p35 regulates neurotransmitter release through phosphorylation and downregulation of P/Q-type voltage-dependent calcium channel activity. J Neurosci 22: 2590–2597.
Treherne JM, Ashford MLJ. 1991. The regional distribution of sulfonylurea binding sites in rat brain. Neuroscience 40: 523–531.
Turnbow MA, Keller RS, Rice KM, Garnar CW. 1994. Dexamethasone down-regulation of insulin receptor substrate-1 in 3T3 L1 adipocytes. J Biol Chem 269: 2516–2520.
Turnbull S, Tabner BJ, El-Agnaf OM, Moore S, Davies Y, et al. 2001. Alpha-synuclein implicated in Parktinson's disease catalyses the formation of hydrogen peroxide in vitro. Free Radic Biol Med 30: 1163–1170.
Turner M, Moran NF, Kopelman MD. 2002. Subcortical dementia. Br J Psychiatry 180: 148–151.
Uchida N, Honjo Y, Johnson KR, Wheelock MJ, Takeichi M. 1996. The catenin/cadherin adhesion system is localized in synaptic junctions bordering transmitter release zone. J Cell Biol 135: 767–779.
Unger J, McNeill TH, Moxley RT, White M, Moss A, et al. 1989. Distribution of insulin receptor-like immuno-reactivity in the rat forebrain. Neuroscience 31: 143–157.
Valverde AM, Teruel T, Navarro P, Benito M, Lorenzo M. 1998. Tumor necrosis factor-α causes insulin receptor substrate-2-mediated insulin resistance and inhibits insulin-induced adipogenesis in fetal brown adipocytes. Endocrinology 139: 1229–1238.
Valverde AN, Mur C, Pon S, Alvarez AM, White MF, et al. 2001. Association of insulin receptor substrate-1 (IRS-1) Y895 with Grb-2 mediates the insulin signalling involved in IRS-1-deficient brown adipocyte mitogenesis. Mol Cell Biol 21: 2269–2280.
van Houten M, Posner BI, Kopriwa BM, Brawer JR. 1979. Insulin binding sites in the rat brain: In vivo localization to the circumventricular organs by quantitative autoradiography. Endocrinology 105: 666–673.
van Houten M, Posner BI, Kopriwa BM, Brawer JR. 1980. Insulin binding sites localized to nerve terminals in rat median eminence and arcuate nucleus. Science 207: 1081–1083.
Vanhaesebroeck B, Alessi DR. 2000. The PIK 3 K-PDK1 connection: More than just a road to PKB. Biochem J 346: 561–576.
Vekrellis K, Ye Z, Qiu WQ, Walsh D, Hartle D, et al. 2000. Neurons regulate extracellular levels of amyloid β-protein via proteolysis by insulin-degrading enzyme. J Neurosci 20: 1657–1665.
Verde C, Pascale MC, Martive G, Lotti LV, Torrisi MR, et al. 1995. Effect of ATP depletion and DTT on the transport of membrane proteins from the endoplasmic reticulum and the intermediate compartment to the Golgi complex. Eur J Cell Biol 67: 267–274.
Villa RF, Gorini A, Hoyer S. 2002. ATPases of synaptic plama membranes from hippocampus after ischemia and recover during aging. Neurochem Res 27: 861–870.
Virkamäki A, Ueki K, Kahn CR. 1999. Protein-protein interaction in insulin signalling and the molecular mechanisms of insulin resistance. J Clin Invest 103: 931–943.
Virsolvy-Vergine A, Leray H, Kuroki S, Lupo B, Dufour M, et al. 1992. Endosulfine, an endogenous peptidic ligand for the sulfonylurea receptor: Purification and partial characterization from ovine brain. Proc Natl Acad Sci USA 89: 6629–6633.
Vlassara H, Brownlee M, Cerami A. 1985. High-affinity H receptor-mediated uptake and degradation of glucose-modified proteins: A potential mechanism for the removal of senescent macromolecules. Proc Natl Acad Sci USA 82: 5588–5592.
Vlassara H, Bucala R, Striker L. 1994. Biology of disease. Pathogenetic effects of advanced glycosylation: Biochemical, biologic, and clinical implications for diabetes and aging. Lab Invest 70: 138–151.
Vogelsberg-Ragaglia V, Schuck T, Trojanowski JQ, Lee VM. 2001. PP2A mRNA expression is quantitatively decreased in Alzheimer's disease hippocampus. Exp Neurol 168: 402–412.
Vosseller K, Sakabe K, Wells L, Hart GW. 2002. Diverse regulation of protein function by 0-GlcNAc: A nuclear and cytoplasmic carbohydrate post-translational modification. Curr Opin Chem Biol 6: 851–857.
Waksman G, Hamel E, Delay-Goyet P, Roques BP. 1986. Neuronal localization of the neutral endopeptidase “enkephalinase” in rat brain revealed by lesions and autoradiography. EMBO J 5: 3165–3166.
Walaas U, Fonnum F. 1980. Biochemical evidence for glutamate as a transmitter in hippocampal efferents to the basal forebrain and hypothalamus in the rat brain. Neuroscience 5: 1691–1698.
Walker D, Kim S, McGeer P. 1998. Expression of complement C4 and C9 genes by human astrocytes. Brain Res 809: 31–38.
Walker D, Lue L, Beach T. 2001. Gene expression profiling of amyloid beta peptide-stimulated human post-mortem brain microglia. Neurobiol Aging 22: 957–966.
Wallace W, Ahlers ST, Gotlib J, Bragin V, Sugar J, et al. 1993. Amyloid precursor protein in the cerebral cortex is rapidly and persistently induced by loss of subcortical innervation. Proc Natl Acad Sci USA 90: 8712–8716.
Wallace WC, Akar CA, Lyons EW. 1997a. Amyloid precursor protein potentiates the neurotrophic activity of NGF. Mol Brain Res 52: 201–212.
Wallace WC, Akar CA, Lyons WE, Kole HK, Egan JE, et al. 1997b. Amyloid precursor protein requires the insulin signaling pathway for neurotrophic activity. Mol Brain Res 52: 213–227.
Wang JZ, Gong CX, Zaidi T, Grundke-Iqbal I, Iqbal K. 1995. Dephosphorylation of Alzheimer paired helical filaments by protein phosphatase-2A and –2B. J Biol Chem 270: 4854–4860.
Watanabe A, Hasegawa M, Suzuki M, Takio K, Morishima-Kawashima M, et al. 1993. In vivo phosphorylation sites in fetal and adult rat tau. J Biol Chem 268: 25712–25717.
Welch WJ, Suhan JP. 1985. Morphological study of the mammalian stress response: Characterization of changes in the cytoplasmic organelles, cytoskeleton, and nucleoli, and appearance of intranuclear actin filaments in rat fibroblasts after heat-shock treatment. J Cell Biol 101: 1198–1211.
Welsh GI, Proud CG. 1993. Glycogen synthase kinase-3 is rapidly inactivated in response to insulin and phosphorylates eukaryotic initiation factor elF-2B. Biochem J 294: 625–629.
Werther GA, Hogg A, Oldfield BJ, McKinley MJ, Figdor R, et al. 1987. Localization and characterization of insulin receptors in rat brain and pituitary gland using in vitro autoradiography and computerized densitometry. Endocrinology 121: 1562–1570.
Westerberg E, Deshpande DK, Wieloch T. 1987. Regional differences in arachidonic acid release in rat hippocampal CA1 and CA3 regions during cerebral ischemia. J Cereb Blood Flow Metab 7: 189–192.
White MF, Kahn CR. 1994. The insulin signalling system. J Biol Chem 269: 1–4.
Whittemore SR, Ebendal T, Larkfors L, Olson L, Seiger A, et al. 1986. Development and regional expression of beta nerve growth factor messenger RNA and protein in the rat central nervous system. Proc Natl Acad Sci USA 83: 817–821.
Wild-Bode C, Yamazaki T, Capell A, Leimer U, Steiner H, et al. 1997. Intracellular generation and accumulation of amyloid β-peptide terminating at amino acid-42. J Biol Chem 272: 16085–16088.
Wilson CA, Doms RW, Lee VMY. 1999. Intracellular APP processing and Aβ production in Alzheimer disease. J Neuropathol Exp Neurol 58: 787–794.
Wong KL, Tyce GM. 1983. Glucose and amino acid metabolicm in rat brain during sustained hypoglycemia. Neurochem Res 8: 401–415.
Wu HC, Lee EHY. 1997. Identification of a rat brain gene associated with aging by PCR differential display method. J Mol Neurosci 8: 13–18.
Wurtman RJ. 1992. Choline metabolism as a basis for the selective vulnerability of cholinergic neurons. Trends Neurosci 15: 117–122.
Wyllie MG, Gilbert JL. 1979. An investigation into the role of synaptic vesicular Mg2 + -ATPase in neurotransmitter release using benzhydryl piperazine. Arch Int Pharmacodyn Ther 241: 4–15.
Xia W, Zhang J, Perez R, Koo EH, Selkoe DJ. 1997. Interaction between amyloid precursor protein and presenilins in mammalian cells: Implications for the pathogenesis of Alzheimer disease. Proc Natl Acad Sci USA 94: 8208–8213.
Xie L, Helmerhorst E, Taddel K, Plewright B, van Bronswijk W, et al. 2002. Alzheimer's β-amyloid peptides compete for insulin binding to the insulin receptor. J Neurosci 22 (RC221): 1–5.
Xu H, Sweeny D, Wang R, Thinakaran G, Lo AC, et al. 1997. Generation of Alzheimer beta-amyloid protein in the trans-Golgi network in the apparent abscence of vesicle formation. Proc Natl Acad Sci USA 94: 3748–3752.
Yan LJ, Sohal RS. 1998. Mitochondrial adenine nucleotide translocase is modified oxidatively during aging. Proc Natl Acad Sci USA 95: 12896–12901.
Yan SD, Chen X, Fu J, Chen M, Zhu H, et al. 1996. RAGE and amyloid-β peptide neurotoxicity in Alzheimer's disease. Nature 382: 685–691.
Yanagisawa M, Planel E, Ishiguro K, Fugita SC. 1999. Starvation induces tau hyperphosphorylation in mouse brain: Implications for Alzheimer's disease. FEBS Lett 461: 329–333.
Yang AJ, Chandswangbhuvana D, Shu T, Henschen A, Glabe CG. 1999. Intracellular accumulation of insoluble, newly snythesized Aβn-42 in amyloid precursor protein-transfected cells that have been treated with Aβ 1–42. J Biol Chem 274: 20650–20656.
Yang Y, Turner RS, Gaut JR. 1998. The chaperone BiP/GRP78 binds to amyloid precursor protein and decreases Abeta 40 and Abeta 42 secretion. J Biol Chem 273: 25552–25555.
Yasojima K, Akiyama H, McGeer EG, McGeer PL. 2001a. Reduced neprilysin in high plaque areas of Alzheimer brain: A possible relationship to deficient degradation of β-amlyoid peptide. Neurosci Lett 297: 97–100.
Yasojima K, McGeer EG, McGeer PL. 2001b. Relationship between β-amlyoid peptide generating molecules and neprilysin in Alzheimer disease and normal brain. Brain Res 919: 115–121.
Yki-Jarvinen H, Virkamaki A, Daniels MC, McClain D, Gottschalk WK. 1998. Insulin and glucosamine infusions increase O-linked N-acetyl-glucosamine in skeletal muscle protein in vivo. Metabolism 47: 449–455.
Yoo BC, Kim SH, Cairns N, Fountoulakis M, Lubec G. 2001. Deranged expression of molecular chaperones in brains of patients with Alzheimer's disease. Biochem Biophys Res Commun 280: 249–258.
Youdim MB. 2003. What have we learnt from CDNA microarray gene expression studies about the role of iron in MPTP induced neurodegeneration and Parkinson's disease? J Neural Transm 65 (Suppl.): 73–88.
Youdim MB, Ben-Shachar D, Riederer P. 1993. The possible role of iron in the etiopathology of Parkinson's disease. Mov Disord 8: 1–12.
Yu G, Chen F, Levesque G, Nishimura M, Zhang DM, et al. 1998. The presenilin 1 protein is a component of a high molecular weight intracellular complex that contains β-catenin. J Biol Chem 273: 16470–16475.
Zahniser NR, Goens MB, Hanaway PJ, Vinych JV. 1984. Characterization and regulation of insulin receptors in rat brain. J Neurochem 42: 1354–1362.
Zaia A, Piantanelli L. 2000. Insulin receptors in the brain cortex of aging mice. Mech Ageing Dev 113: 227–232.
Zhang H, Sternberger NH, Rubinstein LJ, Herman MM, Binder LI, et al. 1989. Abnormal processing of multiple proteins in Alzheimer's disease. Proc Natl Acad Sci USA 86: 8045–8049.
Zhao W, Chen H, Xu H, Moore E, Meiri N, et al. 1999. Brain insulin receptors and spatial memory. J Biol Chem 274: 34893–34902.
Zhao WQ, Chen H, Quon MH, Alkon DL. 2004. Insulin and the insulin receptor in experimental models of learning and memory. Eur J Pharmacol 490: 71–81.
Zhao WQ, Feng G, Alkon DL. 2003. Impairment of phosphatase 2A contributes to the prolonged MAP kinase phosphorylation in Alzheimer's disease fibroblasts. Neurobiol Dis 14: 458–469.
Zhou J, Liyanage U, Medina M, Ho C, Simmons AD, et al. 1997. Presenilin 1 interaction in the brain with a novel member of the Armadillo family. Neuroreport 8: 1489–1494.
Zini S, Tremblay E, Pollard H, Moreau J, Ben-Ari Y. 1993. Regional distribution of sulfonylurea receptors in the brain of rodent and primate. Neuroscience 55: 1085–1091.
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Hoyer, S., Frölich, L. (2007). Dementia: The Significance of Cerebral Metabolic Disturbances in Alzheimer's Disease. Relation to Parkinson's Disease. In: Lajtha, A., Youdim, M.B.H., Riederer, P., Mandel, S.A., Battistin, L. (eds) Handbook of Neurochemistry and Molecular Neurobiology. Springer, New York, NY. https://doi.org/10.1007/978-0-387-30377-2_12
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