Advertisement

Reduced Neuronal Activity is One of the Major Hallmarks of Alzheimer’s Disease

Conference paper
Part of the Research and Perspectives in Alzheimer’s Disease book series (ALZHEIMER)

Abstract

Alzheimer’s disease (AD) is histopathologically characterized by the presence of neuritic plaques (NPs) and cytoskeletal changes (Fig. 1) that are visible as pretangles stained by Alz-50, neurofibrillary tangles (NFT) in the cell bodies of affected neurons, and neuropil threads (Braak et al. 1986) or dystrophic neurites (Kowall and Kosik 1987). Dystrophic neurites are defined as short, thickened, curly, coiled or sometimes hooked fibres observable as the neuritic component of NPs or present in the neuropil outside these structures. Neuropil threads is an alternative term for dystrophic neurites that are not the neuritic component of NPs. To a lesser degree, NPs and cytoskeletal changes can also be observed in aged, nondemented control subjects.

Keywords

Senile Dementia Neuritic Plaque Dystrophic Neurites Neurobiol Aging Cytoskeletal Change 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Akiyama H, Tago H, Itagaki S, McGeer PL (1990) Occurrence of diffuse amyloid deposits in the presubicular parvopyramidal layers in Alzheimer’s disease. Acta Neuropath (Berl) 79: 537 – 544Google Scholar
  2. Allen SJ, Dawbarn D, Wilcock GK (1988) Morphometric immunochemical analysis of neurons in the nucleus basalis of Meynert in Alzheimer’s disease. Brain Res 454: 275 – 281PubMedGoogle Scholar
  3. Andrä K, Abramowski D, Duke M, Probst A, Wiederhold K-H, Bürki K, Goedert M, Sommer B, Staufenbiel M (1996) Expression of APP in transgenic mice: a comparison of neuron-specific promotors. Neurobiol Aging 17: 183 – 190PubMedGoogle Scholar
  4. Armstrong RA, Myers D, Smith CUM (1992) Alzheimer’s disease: Are cellular neurofibrillary tangles linked to beta/A4 formation at the projection sites? Neurosci Res Comm 11: 171 – 177Google Scholar
  5. Armstrong RA, Myers D, Smith CUM (1993) The spatial patterns of plaques and tangles in Alzheimer’s disease do not support the’cascade hypothesis.’ Dementia 4: 16 – 20PubMedGoogle Scholar
  6. Arnold SE, Hyman BT, Flory J, Damasio AR, Van Hoesen GW (1991) The topographical and neuroana-tomical distribution of neurofibrillary tangles and neuritic plaques in the cerebral cortex of patients with Alzheimer’ disease. Cereb Cortex 1: 103 – 106PubMedGoogle Scholar
  7. Arriagada PV, Growdon JH, Hedly-Whyte ET, Hyman BT (1992) Neurofibrillary tangles but not senile plaques parallel duration and severity of Alzheimer’s disease. Neurology 42: 631 – 639PubMedGoogle Scholar
  8. Bancher C, Brunner C, Lassmann H, Budka H, Jellinger K, Wiche G, Grundke-Iqbal I, Iqbal K, Wisnieswski HM (1989) Accumulation of abnormally phosphorylated tau precedes the formation of neurofibrillary tangles in Alzheimer’s disease. Brain Res 477: 90 – 99PubMedGoogle Scholar
  9. Barcikowska M, Wisniewski HM, Bancher C, Grundke-Iqbal I (1989) About the presence of paired helical filaments in dystrophic neurites participating in the plaque formation. Acta Neuropath (Berl) 78: 225 – 231Google Scholar
  10. Bondareff W, Mountjoy CQ, Roth M (1982) Loss of neurons of origin of the adrenergic projection to cerebral cortex (nucleus locus ceruleus) in senile dementia. Neurology 32: 164 – 168PubMedGoogle Scholar
  11. Bouras C, Hof PR, Giannakopoulos P, Michel J-P, Morrison JH (1994) Regional distribution of neurofibrillary tangles and senile plaques in the cerebral cortex of elderly patients: a quantitative evaluation of a one-year autopsy population from a geriatric hospital. Cereb Cortex 4: 138 – 150PubMedGoogle Scholar
  12. Bowen DM, Smith CB, White P, Flack RHA, Carrasco LH, Gedye JL, Davidson AN (1977) Chemical pathology of the organic dementias. II. Quantiative estimation of cellular changes in post-mortem brains. Brain 100: 427 – 453PubMedGoogle Scholar
  13. Braak E, Braak H, Mandelkow E-M (1994) A sequence of cytoskeletal changes related to the formation of neurofibrillary tangles and neuropil threads. Acta Neuropathol (Beri) 8733: 554 - 567Google Scholar
  14. Braak H, Braak E (1990) Alzheimer’s disease: Striatal amyloid deposits and neurofibrillary changes. J Neuropath Exp Neurol 49: 15 – 224Google Scholar
  15. Braak H, Braak E (1991) Neuropathological staging of Alzheimer-related changes. Acta Neuropath (Berl) 82: 239 – 259Google Scholar
  16. Braak H, Braak E, Grundke-Iqbal I (1986) Occurrence of neuropil threads in the senile human brain and in Alzheimer’s disease: a third location of paired helical filaments outside of neurofibrillary tangles and neuritic plaques. Neurosci Lett 65: 351 – 355PubMedGoogle Scholar
  17. Braak H, Braak E, Bohl J, Lang W (1989a) Alzheimer’s disease: amyloid plaques in the cerebellum. J Neurol Sci 93: 277 – 287Google Scholar
  18. Braak H, Braak E, Ohm T, Bohl J (1989b) Alzheimer’s disease: mismatch between amyloid plaques and neuritic plaques. Neurosci Lett 103: 24 – 28Google Scholar
  19. Chan-Palay V, Asan E (1989) Alterations in catecholamine neurons of the locus coeruleus in senile dementia of the Alzheimer type and in Parkinson’s disease with and without dementia and depression. J Comp Neurol 287: 373 – 392PubMedGoogle Scholar
  20. Crystal H, Dickson D, Fuld P, Masur D, Scott R, Mehler M, Masdeu J, Kawas C, Aronson M, Wolfson L (1988) Clinico-pathologic studies in dementia: nondemented subjects with pathologically confirmed Alzheimer’s disease. Neurology 38: 1682 – 1687PubMedGoogle Scholar
  21. Davies L, Wolska B, Hilbich C, Multhaup G, Martins R, Simms G, Beyreuther K, Masters CL (1988) A4 amyloid protein deposition and the diagnosis of Alzheimer’s disease: Prevalence in aged brains determined by immunocytochemistry compared with conventional neuropathologic techniques. Neurology 38: 1688 – 1693PubMedGoogle Scholar
  22. De Lacalle S, Iraizoz I, Ma Conzalo L (1992) Differential changes in cell size and number in topographic subdivisions of human basal nucleus in normal aging. Neuroscience 43: 445 – 456Google Scholar
  23. Delaere P, Duyckaerts C, Masters CL, Beyreuther K (1990) Large amounts of neocortical beta/A4 deposits without neuritic plaques nor tangles in psychometrically assessed, non-demented person. Neurosci Lett 116: 87 – 93PubMedGoogle Scholar
  24. Delaere P, Yi HE, Fayet G, Duyckaerts C, Hauw J-J (1993) Beta/A4 deposits are constant in the brain of the oldest old: an immunohistochemical study of 20 French centenarians. Neurobiol Aging 14: 191 – 194PubMedGoogle Scholar
  25. Dickson DW, Farlo J, Davies P, Crystal H, Fuld P, Yen S-HC (1988) Alzheimer’s disease: A double-labelling immunohistochemical study of senile plaques. Am J Path 132: 86 – 101PubMedGoogle Scholar
  26. Doebler JA, Markesberry WR, Anthony A, Davies P, Scheff SW, Rhoads RE (1988) Neuronal RNA in relation to Alz-50 immunoreactivity in Alzheimer’s disease. Ann Neurol 23: 20 – 24PubMedGoogle Scholar
  27. Duyckaerts C, Hauw J-J, Bastenaire F, Piette F, Poulain C, Rainsard V, Javoy-Agid F, Berthaux P (1986) Laminar distribution of neocortical senile plaques in senile dementia of the Alzheimer type. Acta Neuropathol (Berl) 70: 249 – 256Google Scholar
  28. Duyckaerts C, Delaere P, Poulain V, Brion J-P, Hauw J-J (1988) Does amyloid precede paired helical filaments in the senile plaque? A study of 125 cases with graded intellectual status in aging and Alzheimer disease. Neurosci Lett 91: 354 – 359PubMedGoogle Scholar
  29. Emre M, Geula C, Ransil BJ, Mesulam M-M (1992) The acute neurotoxicity and effects on cholinergic axons of interacerebrally injected β amyloid in the rat brain. Neurobiol Aging 13: 553 – 560PubMedGoogle Scholar
  30. Foster NL, Chase TN, Mansi L, Brooks R, Fedio P, Patronas NJ, Di Chiro G (1984) Cortical abnormalities in Alzheimer’s disease. Ann Neurol 16: 649 – 654PubMedGoogle Scholar
  31. Games D, Adams D, Alessandrini R, Barbour R, Berthelette P, Blackwell C, Carr T, Clemens J, Donaldson T, Gillespie F, Guido T, Hagopian S, Johnson-Wood K, Khan K, Lee M, Liebowitz P, Lieberburg I, Little S, Masliah E, McConlogue L, Montoya-Zavala M, Mucke L, Paganini L, Penniman E, Powe M, Schenk D, Seubert P, Snyder B, Soriano F, Tan H, Vital J, Wadsworth S, Wolozin B, Zhao J (1995) Alzheimer type neuropathology in transgenic mice overexpressing V717F β-amyloid precursor protein. Nature 373: 523 – 527PubMedGoogle Scholar
  32. German DC, Manaye KF, White III CL, Woodward DJ, McIntire DD, Smith WK, Kalaria RN, Mann DMA (1992) Disease-specific patterns of locus coeruleus cell loss. Ann Neurol 32: 667 - 676PubMedGoogle Scholar
  33. Gertz HJ, Schoknecht G, Krüger H, Cervos-Navarro J (1989) Stability of cell size and nucleolar size in tangle-bearing neurons of hippocampus in Alzheimer’s disease. Brain Res 487: 373 – 375PubMedGoogle Scholar
  34. Goudsmit E, Hofman MA, Fliers E, Swaab DF (1990) The supraoptic and paraventricular nuclei of the human hypohalamus in relation to sex, age and Alzheimer’s disease. Neurobiol Aging 11: 529 – 536PubMedGoogle Scholar
  35. Greenberg BD, Savage MJ, Howland DS, Ali SM, Siedlak SL, Perry G, Siman R, Scott RW (1996) APP transgenesis: approaches toward the development of animal models for Alzheimer disease neuropathology. Neurobiol Aging 17: 153 - 171PubMedGoogle Scholar
  36. Guillemette JG, Wong L, Crapper McLachlan DR, Lewis PN (1986) Characterization of messenger RNA from the cerebral cortex of control and Alzheimer-afflicted brain. J Neurochem 47: 987 – 997PubMedGoogle Scholar
  37. Haxby JV, Grady CL, Koss E, Horwitz B, Schapiro M, Friedland RP, Rapoport SI (1988) heterogeneous anterior-posterior metabolic patterns in dementia of the Alzheimer type. Neurology 38: 1853–1863Google Scholar
  38. Hoogendijk WJG, Pool CW, Troost D, Van Zwieten EJ, Swaab DF (1995) Image-analyzer-assisted morphometry of the locus coeruleus in Alzheimer’s disease, Parkinson’s disease and amyotrophic lateral sclerosis. Brain 118: 131 – 143PubMedGoogle Scholar
  39. 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 – 148PubMedGoogle Scholar
  40. Hozumi S, Okawa M, Mishima K, Hishikawa Y, Hori H, Takahashi K (1990) Phototherapy for elderly patients with dementia and sleep-wake rhythm disorders - a comparison between morning and evening light exposure. Japan J Psych Neurol 44: 813 – 814Google Scholar
  41. 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 – 481PubMedGoogle Scholar
  42. Joachim CL, Morris JH, Selkoe DJ (1989) Diffuse senile plaques occur commonly in the cerebellum in Alzheimer’s disease. Am J Pathol 135: 309 – 319PubMedGoogle Scholar
  43. Jucker M, Walker LC, Martin LJ, Kitt CA, Kleinman HK, Ingram DK, Price DL (1992) Age-associated inclusions in normal and transgenic mouse brain. Science 255: 1443 – 1445PubMedGoogle Scholar
  44. Kalus P, Braak H, Braak ER, Bohl J (1989) The presubicular region in Alzheimer’s disease: topography of amyloid deposits and neurofibrillary changes. Brain Res 494: 198 – 203PubMedGoogle Scholar
  45. Kammesheidt A, Boyce FM, Spanoyannis AF, Cummings BJ, Ortegon M, Cotman C, Vaught JL, Neve RL (1992) Deposition of beta/A4 immunoreactivity and neuronal pathology in transgenic mice expressing the carboxy terminal fragment of the Alzheimer amyloid precursor in the brain. Proc Natl Acad Sci USA 89: 10857 – 10861PubMedGoogle Scholar
  46. Kang J, Lemaire H-G, Unterbeck A, Salbaum JM, Masters CL, Grzeschik K-H, Multhaup G, Beyreuther K, Muller-Hill B (1987) The precursor of Alzheimer’s disease amyloid A4 protein resembles a cell-surface receptor. Nature 325: 733 – 736PubMedGoogle Scholar
  47. Katzman R, Terry RD, DeTeresa R, Brown T, Davies P, Fuld P, Renbing X, Peck A (1987) Clinical, pathological and neurochemical changes in dementia, a subgroup with preserved mental status and numerous neocortical plaques. Ann Neurol 23: 138 – 144Google Scholar
  48. Kawabata S, Higgins GA, Gordon JW (1991) Amyloid plaques, neurofibrillary tangles and neuronal loss in brains of transgenic mice overexpressing a C-terminal fragment of human amyloid precursor protein. Nature 354: 476 – 478PubMedGoogle Scholar
  49. Kowall NW, Kosik KS (1987) Axonal disruption and aberrant localization of tau protein characterize the neuropil pathology of Alzheimer’s disease. Ann Neurol 22: 639 – 643PubMedGoogle Scholar
  50. Kowall N, McKee AC, Yankner BA, Beal MF (1992) In vivo neurotoxicity of beta-amyloid [β(l-40)] and β(25–35) fragment. Neurobiol Aging 13: 537 – 542PubMedGoogle Scholar
  51. Kremer HPH (1992) The hypothalamic lateral tuberal nucleus: normal anatomy and changes in neurological diseases. In: Swaab DF, Hofman MA, Mirmiran M, Ravid R, van Leeuwen FW (eds) The human hypothalamus in health and disease. Progress in Brain Research, Vol 93. Elsevier, Amsterdam, pp 249 – 263Google Scholar
  52. Kremer HPH, Swaab DF, Bots GThAM, Fisser B, Ravid R, Roos RAC (1991) The hypothalamic lateral tuberal nucleus in Alzheimer’s disease. Ann Neurol 29: 279 – 284PubMedGoogle Scholar
  53. Kumar A, Newberg A, Alavi A, Berlin J, Smith R, Reivich M (1993) Regional cerebral glucose metabolism in late-life Alzheimer disease: a preliminary positron emission. Proc Natl Acad Sci USA 90: 7019 – 7023PubMedGoogle Scholar
  54. Lee VM, Balin BJ, Otvos L Jr, Trojanowski JQ (1991) A68: a major subunit of paired helical filaments and forms of normal Tau. Science 251: 675 – 678PubMedGoogle Scholar
  55. Levy-Lahad E, Wijsman EM, Nemens E, Anderson L, Goddard KAB, Weber E, Bird TD, Schellenberg GD (1995) A fimilial Alzheimer’s disease locus on chromosome 1. Science 269: 970 – 973PubMedGoogle Scholar
  56. Lowes-Hummel P, Gertz H-J, Ferszt R, Cervos-Navarro J (1989) The basal nucleus of Meynert revised: the nerve cell number decreases with age. Arch Gerontol Geriatrics 8: 21 – 27Google Scholar
  57. Lucassen PJ, Salehi A, Pool CW, Gonatas NK, Swaab DF (1994) Activation of vasopressin neurons in aging and Alzheimer’s disease. J Neuroendocr 6: 673 – 679Google Scholar
  58. Lucassen PJ, Hofman MA, Swaab DF (1995) Increased light intensity prevents the age related loss of vasopressin-expressing neurons in the rat suprachiasmatic nucleus. Brain Res 693: 261 – 266PubMedGoogle Scholar
  59. Malherbe P, Richards JG, Martin JR, Bluethmann H, Maggio J, Huber G (1996) Lack of β-amyloidosis in transgenic mice expressing low levels of familial Alzheimer’s disease missense mutations. Neurobiol Aging 17: 205 – 214PubMedGoogle Scholar
  60. Mann DMA, Jones D (1990) Deposition of amyloid (A4) protein within the brains of persons with dementing disorders other than Alzheimer’s disease and Down’s syndrome. Neurosci Lett 109: 68 – 75PubMedGoogle Scholar
  61. Mann DMA, Neary D, Yates PO, Lincoln J, Snowden JS, Stanworth P (1981) Alterations in protein synthetic capability of nerve cells in Alzheimer’s disease. J Neurosurg Psychiat 44: 97 – 102Google Scholar
  62. Mann DMA, Yates PO, Marcyniuk B (1984) Changes in nerve cells of the nucleus basalis of Meynert in Alzheimer’s disease and their relationship to ageing and to the accumulation of lipofuscin pigment. Mechan Ageing Dev25: 189 – 204Google Scholar
  63. Mann DMA, Yates PO, Marcyniuk B (1985) Some morphometric observations in the cerebral cortex and hippocampus in presenile Alzheimer’s disease, senile dementia of Alzheimer type and Down’s syndrome in middle age. J Neurol Sci 69: 139 – 159PubMedGoogle Scholar
  64. Manning CA, Ragozzino ME, Gold PE (1993) Glucose enhancement of memory in patients with probable senile dementia of the Alzheimer’s type. Neurobiol Aging 14: 523 – 528PubMedGoogle Scholar
  65. Mantione JR, Kleppner SR, Miyazono M, Wertkin AM, Lee VM-Y, Trojanowski JQ (1995) Human neurons that constitutively secrete Aβ do not induce Alzheimer’s disease pathology following transplantation and long-term survival in the rodent brain. Brain Res 671: 333 – 337PubMedGoogle Scholar
  66. Marcus DL, de Leon MJ, Goldman J, Logan J, Christman DR, Wolf AP, Fowler JS, Hunter K, Tsai J, Pearson J, Freedman ML (1989) Altered glucose metabolism in microvessels from patients with Alzheimer’s disease. Ann Neurol 26: 91 – 94PubMedGoogle Scholar
  67. Masters CL, Simms G, Weinman NA, Multhaup G, McDonald BL, Beyreuther K (1985) Amyloid core plaque protein in Alzheimer disease and Down syndrome. Proc Natl Acad Sci USA 82: 4245 – 4249PubMedGoogle Scholar
  68. McKee AC, Kosik KS, Nowall NW (1991) Neuritic pathology and dementia in Alzheimer’s disease. Ann Neurol 30: 156 – 165PubMedGoogle Scholar
  69. Meier-Ruge W, Bertoni-Freddari C, Iwangoff P (1994) Changes in brain glucose metabolism as a key to the pathogenesis of Alzheimer’s disease. Gerontology 40: 246 – 252PubMedGoogle Scholar
  70. Meneilly GS, Hill A (1993) Alterations in glucose metabolism in patients with Alzheimer’s disease. J Am Geriatr Soc 41: 710 – 714PubMedGoogle Scholar
  71. Mesulam MM, Mufson MJ, Levey AI, Wainer BH (1983) Cholinergic innervation of cortex by the basal forebrain: Cytochemistry and cortical connections of the septal area, diagonal band nuclei, nucleus basalis (substantia innominata), and hypothalamus in the rhesus monkey. J Comp Neurol 214: 170 – 197PubMedGoogle Scholar
  72. Mielke R, Herholz K, Grond M, Kessler J, Heiss WD (1994) Clinical deterioration in probable Alzheimer’s disease correlates with progressive metabolic impairment of association areas. Dementia 5: 36 – 41PubMedGoogle Scholar
  73. Mishima K, Okawa M, Hishikawa Y, Hozumi S, Hori H, Takahashi K (1994) Morning bright light therapy for sleep and behavior disorders in elderly patients with dementia. Acta Psychiatr Scand 89: 1 – 7PubMedGoogle Scholar
  74. Morrison JH, Foote SL, O’Conner D, Bloom FE (1982) Laminar, tangential and regional organization of the noradrenergic innervation of monkey cortex: dopamine-beta-hydroxylase immunohistochemistry. Brain Res Bull 9: 309 – 319PubMedGoogle Scholar
  75. Mukaetova-Ladinska EB, Harrington CR, Roth M, Wischik CM (1993) Biochemical and anatomical redistribution of tau protein in Alzheimer’s disease. Am J Pathol 143: 565 – 578PubMedGoogle Scholar
  76. Mullan M, Houlden H, Windelspect M, Fidani L, Lombardi C, Diaz P, Rossor M, Crook R, Hardy J, Duff K, Crawford F (1992) A locus for familial early onset Alzheimer’s disease on the long arm of chromosome 14, proximal to the alpha 1-anti-chymotrypsin gene. Nature Genet 2: 340 – 342PubMedGoogle Scholar
  77. Nakamura S, Takemura M, Ohnishi K, Suenaga T, Nishimura M, Akiguchi I, Kimura J, Kimura T (1993) Loss of large neurons and occurrence of neurofibrillary tangles in the tuberomammillary nucleus of patients with Alzheimer’s disease. Neurosci Lett 151: 196–199PubMedGoogle Scholar
  78. Ogomori K, Kitamoto T, Tateishi J, Sato Y, Suetsugu M, Abe M (1990) Beta-protein amyloid is widely distributed in the central nervous system of patients with Alzheimer’s disease. Am J Pathol 134: 243 – 251Google Scholar
  79. Okawa M, Mishima K, Hishikawa Y, Hozumi S, Hori H, Takahashi K (1991) Circadian rhythm disorders in sleep-waking and body temperature in elderly patients with dementia and their treatment. Sleep 14: 478 – 485PubMedGoogle Scholar
  80. Pearson RCA, Gatter KC, Powell TPS (1983) Retrograde cell degeneration in the basal nucleus in monkey and man. Brain Res 261: 321 – 326PubMedGoogle Scholar
  81. 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’s disease. Proc Natl Acad Sci USA 82: 4531 – 4534PubMedGoogle Scholar
  82. Peppard RF, Martin WRW, Carr GD, Grochowski E, Schulzer M, Guttman M, McGeer PL, Phillips AG, Tsui JKC, Calne DB (1992) Cerebral glucose metabolism in Parkinson’s disease with and without dementia. Arch Neurol 49: 1262 – 1268PubMedGoogle Scholar
  83. Pericak-Vance MA, Bebout JL, Gaskell Jr PC, Yamaoka LH, Hung WY, Alberts MJ, Walker AP, Bartlett RJ, Haynes CA, Welsh KA, Earl NL, Heyman A, Clark CM, Roses AD (1991) Linkage studies in familial Alzheimer disease: evidence for chromosome 19 linkage. Am J Human Genet 48: 1034 – 1050Google Scholar
  84. Powell RR (1974) Psychological effects of exercise therapy in institutionalized geriatric mental patients. J Gerontol 29: 157 – 164PubMedGoogle Scholar
  85. Quon D, Wang Y, Catalano R, Scardina JM, Murakami K, Cordell B (1991) Formation of beta-amyloid protein deposits in brains of transgenic mice. Nature 352: 239 – 241PubMedGoogle Scholar
  86. Regeur L, Jensen GB, Pakkenberg H, Evans SM, Pakkenberg B (1994) No global neocortical nerve cell loss in brains from senile dementia of Alzheimer’s type. Neurobiol Aging 15: 347 – 352PubMedGoogle Scholar
  87. Reiman EM, Caselli RJ, Yun LS, Chen K, Bandy D, Minoshima S, Thibodeau SN, Osborne D (1996) Preclinical evidence of Alzheimer’s disease in persons homozygous for the E4 allele for apolipoprotein E. N Engl J Med 334: 752 – 758Google Scholar
  88. Rinne JO, Paljarvi L, Rinne UK (1987) Neuronal size and density in the nucleus basalis of Meynert in Alzheimer’s disease. J Neurol Sci 79: 67 – 76PubMedGoogle Scholar
  89. Roberts GW, Allsop D, Bruton CJ (1990) The occult aftermath of boxing. J Neurol Neurosurg Psychiatr 24: 173 – 182Google Scholar
  90. Rogers J, Morrison JH (1985) Quantitative morphology and regional and laminar distributions of senile plaques in Alzheimer’s disease. J Neurosci 5: 2801 – 2808PubMedGoogle Scholar
  91. Rossor MN (1993) Molecular pathology of Alzheimer’s disease. J Neurol Neurosurg Psychiatr 56: 583 – 586PubMedGoogle Scholar
  92. Rozemuller JM, Eikelenboom P, Stam FC, Beyreuther K, Masters CL (1989) A4 protein in Alzheimer’s disease; primary and secondary cellular events in extracellular amyloid deposition. J Neuropath Exp Neurol 48: 674 – 691PubMedGoogle Scholar
  93. Rudelli RD, Ambler MW, Wisniewski HM (1984) Morphology and distribution of Alzheimer neuritic (senile) and amyloid plaques in striatum and diencephalon. Acta Neuropathol (Berl) 64: 273 – 381Google Scholar
  94. Sajdel-Sulkowska EM, Marotta CA (1984) Alzheimer’s disease brain: Alterations in RNA levels and in a ribonuclease-inhibitor complex. Science 225: 947 – 949PubMedGoogle Scholar
  95. Salehi A, Lucassen PJ, Pool CW, Gonatas NK, Ravid R, Swaab DF (1994) Decreased neuronal activity in the nucleus basalis of Alzheimer’s disease as suggested by the size of the Golgi apparatus. Neuroscience 59: 871 – 880PubMedGoogle Scholar
  96. Salehi A, Van de Nes JAP, Hofman MA, Gonatas NK, Swaab DF (1995a) Early cytoskeletal changes as shown by Alz-50 are not accompanied by decreased neuronal activity. Brain Res 678: 29 – 39Google Scholar
  97. Salehi A, Ravid R, Gonatas NK, Swaab DF (1995b) Decreased activity of hippocampal neurons in Alzheimer’s disease is not related to the presence of neurofibrillary tangles. J Neuropathol Exp Neurol 54: 704 – 709PubMedGoogle Scholar
  98. Salehi A, Heyn S, Gonatas NK, Swaab DF (1995c) Decreased protein synthetic activity of the hypothalamic tuberomammillary nucleus in Alzheimer’s disease as suggested by a smaller Golgi apparatus. Neurosci Lett 193: 29 – 32PubMedGoogle Scholar
  99. Salmon E, Gregoire MC, Delfiore G, Lemaire C, Degueldre C, Franck G, Comar D (1996) Combined study of cerebral glucose metabolism and [11C]methionine accumulation in probable Alzheimer’s disease using positron emission tomography. J Cerebr Blood Flow Metab 16: 399 – 408Google Scholar
  100. Satlin A, Volicer L, Ross V, Herz L, Campbell S (1992) Bright light treatment of behavioral and sleep disturbances in patients with Alzheimer’s disease. Am J Psychiatr 149: 1028 – 1032PubMedGoogle Scholar
  101. Schellenberg GD, Bird TD, Wijsman EM, Orr HT, Anderson L, Nemens E, White JA, Bonnycastle L, Weber JL, Alonso ME, Potter H, Heston LL, Martin GM (1992) Genetic linkage evidence for a familial Alzheimer’s disease locus on chromosome 14. Science 258: 668 – 671PubMedGoogle Scholar
  102. Scherder E, Bouma A, Steen L, Swaab D (1995a) Peripheral nerve stimulation in Alzheimer’s disease. A meta-analysis. Alz Res 1: 183 – 184Google Scholar
  103. Scherder EJA, Bouma A, Steen AM (1995b) Effects of short-term transcutaneous electrical nerve stimulation on memory and affective behaviour in patients with probable Alzheimer’s disease. Behav Brain Res 67: 211 – 219PubMedGoogle Scholar
  104. Scherder EJA, Bouma A, Steen AM (1995c) Effects of simultaneously applied short-term transcutaneous electrical nerve stimulation and tactile stimulation on memory and affective behaviour of patients with probable Alzheimer’s disease. Behav Neurol 8: 3 – 13Google Scholar
  105. Selkoe DJ (1994) Alzheimer’s disease: a central role for amyloid. J Neuropathol Exp Neurol 53: 438 – 447PubMedGoogle Scholar
  106. Simonian NA, Hyman BT (1993) Functional alterations in Alzheimer’s disease: diminution cytochrome oxidase in the hippocampal formation. J Neuropathol Exp Neurol 52: 580 – 585PubMedGoogle Scholar
  107. Simonian NA, Hyman BT (1994) Functional alterations in Alzheimer’s disease: selective mitochondrial-encoded cytochrome oxidase mRNA in the formation. J Neuropathol Exp Neurol 53: 508 – 512PubMedGoogle Scholar
  108. Standaert DG, Lee VM-Y, Greenberg BD, Lowery DE, Trojanowski JQ (1991) Molecular features of hypothalamic plaques in Alzheimer’s disease. Am J Pathol 139: 681 – 691PubMedGoogle Scholar
  109. St George-Hyslop PH, Haines J, Rogaev, Mortilla M, Vaula G, Pericak-Vance M, Foncin J-F, Montesi M, Bruni A, Sorbi S, Rainero I, Pinessi L, Pollen D, Polinsky R, Nee L, Kennedy J, Macciardi, Rogaeva E, Liang Y, Alexandrova N, Lukiw W, Schlumpf K, Tanzi R, Tsuda T, Farrer L, Cantu J-M, Duara R, Amaducci L, Bergamini L, Gusella, Roses A, Crapper McLachlan D (1992) Genetic evidence for a novel familial Alzheimer’s disease locus on chromosome 14. Nature Genet 2: 330 – 334PubMedGoogle Scholar
  110. Strittmatter WJ, Saunders AM, Schmechel D, Pericak-Vance M, Enghild J, Salvesen GS, Roses AD (1993a) Apolipoprotein E: high-avidity binding to beta-amyloid and increased frequency of type allele in late-onset familial Alzheimer disease. Proc Natl Acad Sci USA 90: 1977 – 1981PubMedGoogle Scholar
  111. Strittmatter WJ, Weisgraber KH, Huang DY, Dong L-M, Salvesen GS, Pericak-Vance M, Schmechel D, Saunders AM, Goldgaber D, Roses AD (1993b) Binding of human apolipoprotein E to synthetic amyloid beta peptide; isoform specific effects and implications for late-onset Alzheimer disease. Proc Natl Acad Sci USA 90: 8098 – 8102Google Scholar
  112. Suzuki K, Katzman R, Korey SR (1965) Chemical studies on Alzheimer’s disease. J Neuropathol Exp Neurol 24: 211 – 214PubMedGoogle Scholar
  113. Swaab DF (1991) Brain aging and Alzheimer’s disease: “wear and tear” versus “use it or lose it”. Neurobiol Aging 12: 317 - 324PubMedGoogle Scholar
  114. Swaab DF, Hofman MA (1988) Sexual differentiation of the human hypothalamus: ontogeny of the sexually dimorphic nucleus of the preoptic area. Dev Brain Res 44: 314 – 318Google Scholar
  115. Swaab DF, Fliers E, Partiman T (1985) The suprachiasmatic nucleus of the human brain in relation to sex, age and dementia. Brain Res 342: 37 – 44PubMedGoogle Scholar
  116. Swaab DF, Grundke-Iqbal I, Iqbal K, Kremer HPH, Ravid R, Van de Nes JAP (1992) Tau and ubiquitin in the human hypothalamus in aging and Alzheimer’s disease. Brain Res 590: 239 – 249PubMedGoogle Scholar
  117. Swerdlow R, Marcus DL, Landman J, Kooby D, Frey W, Freedman ML (1994) Brain glucose metabolism in Alzheimer’s disease. Am J Med Sci 308: 141 – 144PubMedGoogle Scholar
  118. Tagliavini F, Giaccone G, Verga L, Ghiso J, Frangione B, Bugiani O (1991) Alzheimer patients: preamyloid deposits are immunoreactive with antibodies to extracellular domains of the amyloid precursor protein. Neurosci Lett 128: 117 – 120PubMedGoogle Scholar
  119. Tate B, Aboody-Guterman KS, Morris AM, Walcott EC, Majocha RE, Marotta CA (1992) Disruption of circadian regulation by brain grafts that overexpresses Alzheimer β/A4 amyloid. Proc Natl Acad Sci USA 89: 7090 – 7094PubMedGoogle Scholar
  120. Taylor GR, Carter GI, Crow TJ, Johnson JA, Fairbairn AF (1986) Recovery and measurement of specific RNA species from tissue: a general reduction in Alzheimer’s disease detected by hybridization. Exp Mol Pathol 44: 111 – 116PubMedGoogle Scholar
  121. Terry RD, Hansen LA, DeTeresa R, Davies P, Tobias H, Katzman R (1987) Senile dementia of the Alzheimer type without neocortical neurfibrillary tangles. J Neuropath Exp Neurol 46: 262 – 268PubMedGoogle Scholar
  122. Van Broeckhoven C, Backhovens H, Cruts M, De Winter G, Bruyland M, Cras P, Martin J-J (1992) Mapping of a gene predisposing to early-onset Alzheimer’s disease to chromosome 14q24.3. Nature Genet 2: 335 – 339PubMedGoogle Scholar
  123. Van de Nes JAP, Kamphorst W, Ravid R, Swaab DF (1993) The distribution of Alz-50 immunoreactivity in the hypothalamus and adjoining areas of Alzheimer’s disease patients. Brain 116: 103 – 115PubMedGoogle Scholar
  124. Van de Nes JAP, Kamphorst W, Swaab DF (1994) Arguments for and against the primary amyloid local induction hypothesis of the pathogenesis of Alzheimer’s disease. Ann Psychiat 4: 95 – 111Google Scholar
  125. Van der Woude PF, Goudsmit E, Wierda M, Purba JS, Hofman MA, Bogte H, Swaab DF (1995) No vasopressin cell loss in the human paraventricular and supraoptic nucleus during aging and in Alzheimer’s disease. Neurobiol Aging 16: 11 – 18PubMedGoogle Scholar
  126. West MJ, Coleman PD, Flood DG, Tronsoco JC (1994) Differences in the pattern of hippocampal neuronal loss in normal ageing and Alzheimer’s disease. Lancet 344: 769 – 772PubMedGoogle Scholar
  127. Whitehouse PJ, Price DL, Struble RG, Clark AW, Coyle JT, Delong MR (1982) Alzheimer’s disease and senile dementia: loss of neurons in the basal forebrain. Science 215: 1237 – 1239PubMedGoogle Scholar
  128. Whitehouse PJ, Hedreen JC, White CL, Clark AW, Price DL (1983) Neuronal loss in the basal forebrain cholinergic system is more marked in Alzheimer’s disease than in senile dementia of the Alzheimer type. Ann Neurol 14: 149Google Scholar
  129. Wirak DO, Bayney R, Ramabhadran TV, Fracasso RP, Hart JT, Hauer PE, Hsiau P, Pekar SK, Scangos GA, Trapp BD, Unterbeck AJ (1991) Deposits of amyloid protein in the central nervous system of transgenic mice. Science 253: 1 – 2Google Scholar
  130. Wisniewski HM, Wegiel J (1995) The neuropathology of Alzheimer’s disease. Neuroimaging Clin N Am 5 (1): 45 – 57PubMedGoogle Scholar
  131. Witting W, Kwa IH, Eikelenboom P, Mirmiran M, Swaab DF (1990) Alterations in the circadian rest-activity rhythm in aging and Alzheimer’s disease. Biol Psychiatr 27: 563 – 572Google Scholar
  132. Witting W, Mirmiran M, Bos NP, Swaab DF (1993) Effect of light intensity on diurnal sleep-wake distribution in young and old rats. Brain Res Bull 30: 157 – 162PubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1997

Authors and Affiliations

  1. 1.Netherlands Institute for Brain ResearchAmsterdamThe Netherlands

Personalised recommendations