Advertisement

Neue Behandlungsansätze bei der Alzheimer-Demenz

  • M. Rösler
  • A. Heidrich

Zusammenfassung

Die folgende übersicht befaβt sich mit neuen medikamentösen Behandlungsstrategien, die zur Therapie kognitiver Symptome bei der Alzheimer-Demenz (DAT) erprobt werden. Die verschiedenen Ansätze sind, soweit dies möglich war, nach dem Gesichtspunkt der jeweiligen ätiopathogenetischen Modellvorstellungen im Zusammenhang mit der Alzheimer-Demenz (DAT) geordnet worden.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

Literatur

  1. Adamus W, Leonard J, Tröger W (1995) Phase I clinical trial with WAL 2014, a new muscarinic agonist for the treatment of Alzheimer’s disease. Life Sci 56: 883–890PubMedCrossRefGoogle Scholar
  2. Aisen P (1997) Inflammation and Alzheimer’s disease: mechanisms and therapeutic strategies. Gerontology 43: 143–149PubMedCrossRefGoogle Scholar
  3. Aisen P, Marin D, Altstiel L, Goodwin C, Baruch B, Jacobson R, Rayn T, Davis K (1996) A pilot study of prednisone in Alzheimer’s disease. Dementia 7: 201–206PubMedGoogle Scholar
  4. Augustinsson L, Blennow K, Blomstrandt C, Brane G, Ekman R, Fredman P, Karlsson I, Kihlgren M, Lehmann W, Lekman A, Mansson J, Ramström I, Wallin A, Wikkelsö C, Gottfries C, Svennerholm L (1997) Intracerebroventricular administration of GM1 ganglioside to presenile Alzheimer patients. Dementia 8: 26–33Google Scholar
  5. Auteri A, Mosca A, Lattuada N, Luzzana M, Zecca L, Radice D, Imhimbo B (1993) Pharmacodynamics and pharmacokinetics of eptastigmine in elderly subjects. Eur J Clin Pharmacol 45: 373–376PubMedCrossRefGoogle Scholar
  6. Bauer J, Berger M (1993) Neuropathologische, immunologische und psychobiologische Aspekte der Alzheimer-Demenz. Fortschr Neural Psychiat 61: 225–240CrossRefGoogle Scholar
  7. Bauer J, Strauss S, Schreiter-Gasser U, Ganter U, Schlegel P, Witt I, Yolk B, Berger M (1991) Interleukin-6 and alpha-2-macroglobulin indicate an acute phase response in Alzheimer’s disease cortices. FEBS Lett 285: 111–114PubMedCrossRefGoogle Scholar
  8. Bencherif M, Lovette M, Fowler K, Arrington S, Reeves L, Cladwell W, Lippiello P (1996) RJR-2403: a nicotinic agonist with CNS selectivity. I. In vitro characterization. J Pharmacol Exp Ther 279: 1413–1421PubMedGoogle Scholar
  9. Birge S (1996) Is there a role for estrogen replacement therapy in the prevention and treatment of dementia? J Am Geriatr Soc 44: 865–870PubMedGoogle Scholar
  10. Birkmayer J (1996) Coenzyme nicotinamide adenine dinucleotide. New therapeutic approach for improving dementia of the Alzheimer type. Ann Clin Lab Sci 26: 1–9PubMedGoogle Scholar
  11. Blum-Degen D, Müller T, Kuhn W, Gerlach M, Przuntek H, Riederer P (1995) Interleukin-1β and interleukin-6 are elevated in the cerebrospinal fluid of Alzheimer’s and de novo Parkinson’s disease patients. Neurosci Lett 202: 17–20PubMedCrossRefGoogle Scholar
  12. Bodick N, Offen W, Levey A, Cutler N, Gauthier S, Satlin A, Shannon H, Tollefson G, Rasmussen K, Bymaster F, Hurley D, Potter W, Paul S (1997a) Effects of Xanomeline, a selective muscarinic receptor agonist, on cognitive function and behavioral symptoms in Alzheimer disease. Arch Neurol 54: 465–473PubMedCrossRefGoogle Scholar
  13. Bodick N, Lucas R, Offen W (1997b) Transdermal delivery of xanomeline, an M1/M4 agonist in development for Alzheimer’s disease. Abstract, 4th Congress, European Society for Clinical Neuropharmacology, EilatGoogle Scholar
  14. Bodovitz S, Falduto M, Frail D, Klein W (1995) Iron levels modulate α-secretase cleavage of amyloid precursor protein. J Neurochem 64: 307–315PubMedCrossRefGoogle Scholar
  15. Breitner J (1996) Inflammatory processes and antiinflammatory drugs in Alzheimer’s disease: a current appraisal. Neurobiol Aging 17: 789–794PubMedCrossRefGoogle Scholar
  16. Breitner J, Gau B, Welsh K, Plassman B, Mcdonald W, Helms M, Anthony J (1994) Invers association of anti-inflammatory treatments and Alzheimer’s disease: initial results of a co-twin control study. Neurology 44: 227–232PubMedCrossRefGoogle Scholar
  17. Brioni J, O’Neill A, Kim D, Buckley M, Decker M, Arneric S (1994) Anxiolytic-like effects of a novel cholinergic channel activator ABT-418. J Pharmacol Exp Ther 271: 353–361PubMedGoogle Scholar
  18. Bruno G, Mohr E, Gillespie M, Fedio R, Chase T (1986) Muscarinic agonist therapy of Alzheimer’s disease. A clinical trial of RS-86. Arch Neurol 43: 659–661Google Scholar
  19. Bruno G, Scaccianoce S, Bonamini M, Patacchioli F, Cesarino F, Grassini P, Sorrentino E, Angelucci I, Lenzi G (1995) Acetyl-L-carnitine in Alzheimer disease: a short-term study on CSF neurotransmitters and neuropeptides. Alzheimer Dis Assoc Disord 9: 128–131PubMedGoogle Scholar
  20. Buccafusco J, Jackson W, Terry A, Marsh K, Decker M, Arneric S (1995) Improvement in performance of a delayed matching-to-sam-ple task by monkeys following ABT-418: a novel cholinergic channel activator for memory enhancement. Psychopharmacology (Berl) 120: 256–266CrossRefGoogle Scholar
  21. Burnes A, Murphy D (1996) Protection against Alzheimer’s disease? Lancet 348: 420–421CrossRefGoogle Scholar
  22. Canal N, Imbimbo BP, for the Eptastigmine Study Group (1996) Relationship between pharmacodynamic activity and cognitive effects of eptastigmine in patients with Alzheimer’s disease. Clin Pharmacol Ther 60: 218–228PubMedCrossRefGoogle Scholar
  23. Carta A, Calvani M, Bravi D, Bhuachalla SN (1993) Acetyl-L-carnitine and Alzheimer’s disease: pharmacological considerations beyond the cholinergic sphere. Ann NY Acad Sci 695: 324–326PubMedCrossRefGoogle Scholar
  24. Cella S, Imhimbo B, Pieretti F, Müller E (1993) Eptastigmine augments basal and GHRH-stimulated growth hormone release in young and old dogs. Life Sci 53: 389–395PubMedCrossRefGoogle Scholar
  25. Christie M (1981) Physostigmine and arecoline: effects of intravenous infusions in Alzheimer’s presenile dementia. Br J Psychiatry 138: 46–50PubMedCrossRefGoogle Scholar
  26. Cooper JM, Wischik C, Schapira A (1993) Mitochondrial function in Alzheimer’s disease. Lancet 341: 969–970PubMedCrossRefGoogle Scholar
  27. Crapper McLachlan D, Dalton A, Kruck T, Bell M, Smith W, Kalow W, Andrews D (1991) Intramuscular desferrioxamine in patients with Alzheimer’s disease. Lancet 337: 1304–1308PubMedCrossRefGoogle Scholar
  28. Cutler N, Sramek J, Seifert R, Conrad J, Wardle T (1995) The safety and tolerance of xanomeline tartrate, a specific cholinergic agonist, in patients with Alzheimer’s disease. In: Hanin I et al. (eds) Alzheimer’s and Parkinson’s diseases. Plenum, New York, pp 479–483Google Scholar
  29. Cutler N, Forrest M, Mengel H, Sramek J (1997) A bridging study of the muscarinic compound Lu-25-109 in patients with probable Alzheimer’s disease. Abstract, 4lth Oholo Conference, EilatGoogle Scholar
  30. Damaj M, Creasy K, Welch S, Rosecrans J, Aceto M, Martin B (1995) Comparative pharmacology of nicotine and ABT-418, a new nicotinic agonist. Psychopharmacology (Berl) 120: 483–490CrossRefGoogle Scholar
  31. Davis D, Hollander E, Davidson M, Davis B, Mohs R, Horvath T (1987) Induction of depression with oxotremorine in patients with Alzheimer’s disease. Am J Psychiatry 144: 468–471PubMedGoogle Scholar
  32. Davis R, Doyle P, Carroll R, Emmerling M, Jaen J (1995) Cholinergic therapies for Alzheimer’s disease. Palliative or disease altering? Arznei-mittelforschung/Drug Res 45: 425–431Google Scholar
  33. Dawson G, Iversen S (1993) The effects of novel Cholinesterase inhibitors and selective muscarinic receptor agonists in tests of reference and working memory. Behav Brain Res 57: 143–153PubMedCrossRefGoogle Scholar
  34. Decker M, Curzon P, Brioni J, Arneric S (1994a) Effects of ABT-418, a novel cholinergic channel ligand, on place learning in septal-le-sioned rats. Eur J Pharmacol 261: 217–222PubMedCrossRefGoogle Scholar
  35. Decker M, Brioni J, Sullivan J, Buckley M, Radek R, Raskiewicz J, Kang C, Kim D, Giardina W, Wasicak J et al. (1994b) (S)-3-methyl-5-(1-methyl-2-pyrrolidinyl)isoxazole (ABT 418): a novel cholinergic ligand with cognition-enhancing and anxiolytic activities. II. In vivo characterization. J Pharmacol Exp Ther 270: 319–328PubMedGoogle Scholar
  36. Domeney AM (1994) Angiotensin converting enzyme inhibitors as potential cognitive enhancing agents. J Psychiatry Neurosci 19: 46–50PubMedGoogle Scholar
  37. Doods N, Quirion R, Mihm G, Engel W, Rudolf K, Entzeroth M, Schiavi G, Ladinsky H, Bechtel W, Ensinger H, Mendla K, Eberlein W (1993) Therapeutic potentials of CNS-active M2 antagonists: novel structures and pharmacology. Life Sci 52: 497–503PubMedCrossRefGoogle Scholar
  38. Dunnett S (1995) Neural transplantation in animal models of dementia. Eur J Neurosci 2: 567–587CrossRefGoogle Scholar
  39. Eckols K, Bymaster F, Mitch C, Shannon H, Ward J, DeLapp N (1995) The muscarinic Ml agonist xanomeline increases soluble amyloid precursor protein release from chines hamster ovarymi cells. Life Sci 57: 1183–1190PubMedCrossRefGoogle Scholar
  40. Eglen R, Watson N (1996) Selective muscarinic receptor agonists and antagonists. Pharmacol Toxicol 78: 59–68PubMedCrossRefGoogle Scholar
  41. Ensinger H, Doods H, Immel-Sehr A, Kuhn F, Lambrecht G, Mendia K (1993) WAL 2014 — a muscarinic agonist with preferential neuron-stimulating properties. Life Sci 52: 473–480PubMedCrossRefGoogle Scholar
  42. Fahnestock M, Scott SA, Jette N, Weingartner JA, Crutcher KA (1996) Nerve growth factor mRNA and protein levels measured in the same tissue from normal and Alzheimer’s disease parietal cortex. Mol Brain Res 42: 175–178PubMedCrossRefGoogle Scholar
  43. Farde L, Suhara T, Halldin C, Nyback H, Nakashima Y, Swahn C, Karlsson P, Ginovart N, Bymaster F, Shannon H, Foged C, Suzdak P, Sauerberg P (1996) Pet study of the Ml-agonist (HC)xanomeline and (llc)butylthio-TZTP in monkey and man. Dementia 7: 187–195PubMedGoogle Scholar
  44. Fillit H, Weinreb H, Cholst I, Luine V, Mcewen B, Amador R, Zabriskie J (1986) Observations in a preliminary open trial of estradiol therapy for senile dementia-Alzheimer’s type. Psychoneuroendocrinology 11: 337–345PubMedCrossRefGoogle Scholar
  45. Fischer P, Götz M, Danielcyk W, Gsell W, Riederer P (1997) Blood transferrin and ferritin in Alzheimer’s disease. Life Sci 60: 2273–2278PubMedCrossRefGoogle Scholar
  46. Fisher L (1995) Engeneered cells: a promising therapeutic approach for neural disease. Rest Neurol Neurosci 8: 49–57Google Scholar
  47. Fisher A, Heldman E, Gurwitz D, Haring R, Mmeshulam H, Brandeis R, Pittel Z, Marciano D, Sapir M, Barak D, Vogel Z, Karton Y (1995) New Ml agonists: selective signaling, neuro-trophic-like and cognitive effects — implications in the treatment of Alzheimer’s disease. In: Hanin I et al. (eds) Alzheimer’s and Parkinson’s disease. Plenum, New York, pp 449–455Google Scholar
  48. Flynn DD, Ferrari-DiLeo G, Mash DC, Levey AI (1995) Differential regulation of molecular subtypes of muscarinic receptors in Alzheimer’s disease. J Neurochem 64: 1888–1891PubMedCrossRefGoogle Scholar
  49. Fourrier A, Letenneur L, Begaud B, Dartigues J (1996) Nonsteroidal antiinflammatory drug use and cognitive function in the elderly. Inconclusive results from a population-based cohort study. J Clin Epidemiol 49: 1201PubMedCrossRefGoogle Scholar
  50. Gerlach M, Ben-Shachar D, Riederer P, Youdim MBH (1994) Altered brain metabolism of iron as a cause of neurodegenerative diseases? J Neurochem 63: 793–807PubMedCrossRefGoogle Scholar
  51. Giacobini E, Mori F, Lai C (1996) The effect of Cholinesterase inhibitors on the secretion of APPs from the brain cortex. Ann NY Acad Sci 777: 393–398PubMedCrossRefGoogle Scholar
  52. Giulian D, Haverkamp L, Li J, Karshin W, Yu J, Tom D, Li X, Kirkpatrick J (1995) Senile plaques stimulate microglia to release a neurotoxin found in Alzheimer brain. Neurochem Int 27: 119–137PubMedCrossRefGoogle Scholar
  53. Gorini A, Ghigini B, Villa R (1996) Acety-cholinesterase activity of synaptic plasma membranes during aging: effect of L-acetylcarnitine. Dementia 7: 147–154PubMedGoogle Scholar
  54. Graves A, White E, Koepsell T (1990) A case control study of Alzheimer’s disease. Ann Neurol 28: 766–774PubMedCrossRefGoogle Scholar
  55. Green PS, Gridley KE, Simpkins JW (1996) Estradiol protects against β-amyloid (25–35)-in-duced toxicity in SK-N-SH human neuroblastoma cells. Neurosci Lett 218: 165–168PubMedCrossRefGoogle Scholar
  56. Griffin W, Stanley I, Ling C, White L, Macleod V, Perrot L, White C, Araoz C (1989) Brain inter-leukin 1 and S-100 immunoreactivity are elevated in Down syndrome and Alzheimer disease. Proc Natl Acad Sci 86: 7611–7615PubMedCrossRefGoogle Scholar
  57. Griffith P, Crossmann A (1993) Distribution of iron in the basal ganglia and neocortex in postmortem tissue in Parkinson’s disease and Alzheimer’s disease. Dementia 4: 61–65Google Scholar
  58. Grodstein F, Stampfer MJ, Colditz GA, Willett WC, Manson JE, Joffe M, Rosner B, Fuchs C, Hankinson SE, Hunter DJ, Hennekens CH, Speizer FE (1997) Postmenopausal hormone therapy and mortality. N Engl J Med 336: 1769–1775PubMedCrossRefGoogle Scholar
  59. Growdon J (1997) Muscarinic agonists in Alzheimer’s disease. Life Sci 60: 993–998PubMedCrossRefGoogle Scholar
  60. Guez D, Neuman E, Malbezin M (1995) Pharmacodynamic and early clinical studies with S12024 in Alzheimer’s disease. In: Levy R, Howard R (eds) Developments in dementia and functional disorders in the elderly. Whrightson, Petersfield, pp 111–119Google Scholar
  61. Hagino N, Ohkura T, Isse K, Akasawa K, Hamamoto M (1995) Estrogen in clinical trial for dementia of Alzheimer type. In: Hanin I et al. (eds) Alzheimer’s and Parkinson’s disease. Plenum, New York, pp 512–523Google Scholar
  62. Hall ED (1997) Lazaroids: mechanisms of action and implications for disorders of the CNS. Neuroscientist 3: 42–51Google Scholar
  63. Halliwell B (1992) Reactive oxygen species and the central nervous system. J Neurochem 59: 1609–1623PubMedCrossRefGoogle Scholar
  64. Hellström-Lindahl E, Zhang C, Nordberg A (1996) Expression of nicotinic receptor subunit mRNAs in lymphocytes from normal and patients with Alzheimer’s disease. Alzheimer’s Res 3: 29–36Google Scholar
  65. Henderson VW, Paganini-Hill A, Emanuel CK, Dunn ME, Dunn J, Buckwalter G (1994) Estrogen replacement therapy in older women: comparisons between Alzheimer’s disease cases and nondemented control subjects. Arch Neurol 51: 896–900PubMedCrossRefGoogle Scholar
  66. Henderson A, Jorm A, Christensen H, Jacomb P, Körten A (1997) Aspirin, antiinflammatory drugs and risk of dementia. Int J Ger Psychiat 12: 926–930CrossRefGoogle Scholar
  67. Hollander E, Davidson M, Mohs R, Horvath T, Davis B, Zemishlany Z, Davis K (1987) RS 86 in the treatment of Alzheimer’s disease: cognitive and biological effects. Biol Psychiat 22: 1067–1078PubMedCrossRefGoogle Scholar
  68. Honjo H, Ogino Y, Naitoh K, Urabe M, Kitawaki J, Yasuda J, Yamamoto T, Ishihara S, Okada H, Yonezawa T, Hayashi K, Nambara T (1989) In vivo effects by estrogene sulfate on the central nervous system-senile dementia (Alzheimer’s type). J Steroid Biochem 34: 521–525PubMedCrossRefGoogle Scholar
  69. Honjo H, Tamura T, Matsumoto Y, Kawata M, Ogino Y, Tanaka K, Yamamoto T, Ueda S, Okada H (1992) Estrogen as a growth factor to central nervous cells. Estrogen treatment promotes development of acetylcholinesterase-positive basal forebrain neurons transplanted in the anterior eye chamber. J Steroid Biochem Mol Biol 41: 633–635PubMedCrossRefGoogle Scholar
  70. Honjo H, Tanaka K, Kashigawa T, Urabe M, Okada H, Hayashi M, Hayashi K (1995) Senile dementia Alzheimer’s type and estrogen. Horm Metab Res 27: 204–207PubMedCrossRefGoogle Scholar
  71. Hoyer S (1994) Neurodegeneration, Alzheimer’s disease, and beta-amyloid toxicity. Life Sci 55: 1977–1983PubMedCrossRefGoogle Scholar
  72. Hoyer S (1996) Oxidative metabolism deficiencies in brains of patients with Alzheimer’s disease. Acta Neurol Scand [Suppl] 165: 18–24CrossRefGoogle Scholar
  73. Hoyer S (1997) Models of Alzheimer’s disease: cellular and molecular aspects. In: Mizuno Y, Youdim B, Calne D, Horowski R, Poewe W, Riederer P (eds) Advances in research on neurodegeneration, vol 3 amp; 4. Springer, Wien New York, pp 11–21CrossRefGoogle Scholar
  74. 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 and incipient early-onset cases. J Neural Transm 3: 1–14CrossRefGoogle Scholar
  75. Hoyer S, Müller D, Plaschke K (1994) Desensi-tiziation of brain insulin receptor. Effect on glucose/energy and related metabolism. J Neural Transm [Suppl] 44: 259–268Google Scholar
  76. Huff F (1996) Preliminary evaluation of besipirdine for the treatment of Alzheimer’s disease. Besipirdine study group. Ann NY Acad Sci 777: 410–414PubMedCrossRefGoogle Scholar
  77. Huff F, Antuono P, Delagandara J, McDonald M, Cutler M, Cohen S, Green R, Zemlan F, Crismon M, Alter M, Shipley J, Reichman W (1996) A treatment and withdrawal trial of besipirdine in Alzheimer disease. Alzheimer Dis Assoc Disord 10: 93–102PubMedCrossRefGoogle Scholar
  78. Imagawa M (1991) Therapy with a combination of coenzyme Q10, vitamin B6 and iron for Alzheimer’s disease and senile dementia of Alzheimer type. In: Iqbal K, McLachlan DRC, Winblad B, Wisniewski H (eds) Alzheimer’s disease: basic mechanisms, diagnosis and therapeutic strategies. Wiley, Chichester, pp 649–651Google Scholar
  79. Jaffe A, ToraN-Allerand C, Greengard P, Gandy S (1994) Estrogen regulates metabolism of Alzheimer Amyloid β Precursor Protein. J Biol Chem 269: 13065–13068PubMedGoogle Scholar
  80. Janiri L, Falcone M, Persico A, Tempesta E (1991) Activity of L-carnitine and acetyl-L-carnitine on cholinoceptive neocortical neurons of the rat in vivo. J Neurotrans 86: 135–146Google Scholar
  81. Jellinger KA (1999) NADH (Nikotinsäure-Ade-nin-Dinukleotid) und M. Alzheimer. Neuropsychiatrie 13: 85–87Google Scholar
  82. Jenkinson M, Bliss M, Brain A, Scott D (1989) Rheumatoid arthritis and senile dementia of the Alzheimer’s type. Br J Rheumatol 28: 86–88PubMedCrossRefGoogle Scholar
  83. Kalaria R (1993) The immunopathology of Alzheimer’s disease and some related disorders. Brain Pathol 3: 333–347PubMedCrossRefGoogle Scholar
  84. Katsuhito M, Hirobumi A, Kyozo H, Huydens R, Nuyens R, Cornelissen F, Geerts H (1993) Sabeluzole potentiates the effect of nerve growth factor on survival and differentiation in PC 12 cells and sympathetic neurons. Neurodegeneration 2: 173–181Google Scholar
  85. Kawas C, Resnick S, Morrison A, Brookmeyer R, Corrada M, Zonderman A, Bacal C, Donnell Lingle D, Metter E (1997) A prospective study of estrogen replacement therapy and the risk of developing Alzheimer’s disease: The Baltimore Longitudinal Study of Aging. Neurology 48: 1517–1521PubMedCrossRefGoogle Scholar
  86. Kuiper M, Mulder C, Van Kamp G, Scheltens P, Wolters E (1994) Cerebrospinal fluid ferritin levels of patients with Parkinon’s disease, Alzheimer’s disease, and multiple system atrophy. J Neural Transm [PD-Sect] 7: 109–114CrossRefGoogle Scholar
  87. Kumar R, Orgogozo J (1997) Efficacy and safety of SB 202026 as a symptomatic treatment for Alzheimer’s disease. Neurosci 20:677–685Google Scholar
  88. Kumar R, Cedar E, Clark M, Loudon J, McCafferty J (1996) Muscarinic partial agonists in the symptomatic treatment of Alzheimer’s disease. In: Becker K, Giacobini E (eds) Alzheimer disease: from molecular biology to therapy. Birkhäuser, Boston, pp 299–303Google Scholar
  89. Lassmann H, Aben I (1997) Immunologie der degenerativen Demenzen. In: Rösler M, Retz W, Thome J (Hrsg) Alzheimer Krankheit. Beltz, Weinheim, S 152–159Google Scholar
  90. Lerner A, Koss E, Debanne S, Rowland D, Smyth K, Friedland R (1997) Smoking and oestrogen-replacement therapy as protective factors for Alzheimer’s disease. Lancet 349: 403–404PubMedCrossRefGoogle Scholar
  91. Lippiello P, Bencherif M, Gray J, Peters S, Grigoryan G, Hodges H, Collins A (1996) RJR-2403. a nicotinic agonist with CNS selectivity. II. In vivo characterization. J Pharmacol Exp Ther 279: 1422–1429PubMedGoogle Scholar
  92. Livingston G, Sax K, McLenahan Z, Blumenthal E, Foley K, Willison J, Mann A, James I (1991) Acetyl-L-carnitine in dementia. Int J Ger Psychiat 6: 853–860CrossRefGoogle Scholar
  93. Mantyh P, Ghilardi J, Rogers S, DeMasters E, Allen C, Stimson E, Maggio J (1993) Aluminum, iron, and zinc ions promote aggregation of physiological concentrations of β-amyloid peptide. J Neurochem 61: 1171–1174PubMedCrossRefGoogle Scholar
  94. Martyn CN, Osmond C, Edwardson JA (1989) Geographical relation between Alzheimer’s disease and aluminium in drinking water. Lancet i: 59–62Google Scholar
  95. Masliah E, Terry RD, Alford M, DeTeresa R, Hansen LA (1991) Cortical and subcortical patterns of synaptophysinlike immunoreactivity in Alzheimer’s disease. Am J Pathol 138: 235–246PubMedGoogle Scholar
  96. Masters CL, Simms G, Weinman NA, Multaup G, McDonald BL, Beyreuther K (1985) Amyloid plaque core protein in Alzheimer disease and Down syndrome. Proc Natl Acad Sci USA 82: 4245–4249PubMedCrossRefGoogle Scholar
  97. Maurer I, Zierz S, Möller H-J (1995) Cytochrome c oxidase in Alzheimer’s disease. Neurology 45: 1423PubMedCrossRefGoogle Scholar
  98. McBee W, Dailey M, Dugan E, Shumaker S (1997) Hormone replacement therapy and other potential treatments for dementias. Endocrinol Metab Clin North Am 26: 329–345PubMedCrossRefGoogle Scholar
  99. MCgeer P, MCgeer E, Rogers J, Sibley J (1990) Anti-inflammatory drugs and Alzheimer’s disease. Lancet 335: 1037CrossRefGoogle Scholar
  100. McKinney M, Coyle J (1991) The potential for muscarinic receptor subtype-specific pharmacotherapy for Alzheimer’s disease. Mayo Clin Proc 66: 1225–1237PubMedCrossRefGoogle Scholar
  101. Medina A, Bodick N, Goldberger A, Mac Mahon M, Lipsitz L (1997) Effects of central muscarinic-1 receptor stimulation on blood pressure regulation. Hypertension 29: 828–834PubMedCrossRefGoogle Scholar
  102. Miller T, Fong K, Tinklenberg J (1993) An ACTH 4–9 analog (ORG 2766) and cognitive performance: high-dose efficacy and safety in dementia of the Alzheimer’s type. Biol Psychiatry 33: 307–309PubMedCrossRefGoogle Scholar
  103. Mori F, Lai C, Fusi F, Giacobini E (1995) Cholinesterase inhibitors increase secretion of APPs in rat brain cortex. Neuroreport 6: 633–636PubMedCrossRefGoogle Scholar
  104. Mortel K, Meyer J (1995) Lack of postmenopausal estrogen replacement therapy and the risk of dementia. J Neuropsychiatry Clin Neurosci 7: 334–337PubMedGoogle Scholar
  105. Mufson E, Connor J, Kordower J (1995) Nerve growth factor in Alzheimer’s disease: defective retrograde transport to nucleus basalis. NeuroReport 6: 1063–1066PubMedCrossRefGoogle Scholar
  106. Muir J, Dunnel S, Robins T, Everitt B (1992) At-tentional functions of the forebrain cholinergic systems: effects of ventricular hemicholinium, physostigmine, basal forebrain lesions and intracortical grafts on a multiple-choice serial reaction time task. Exp Brain Res 89: 611–622PubMedCrossRefGoogle Scholar
  107. Mutisya EM, Bowling AC, Beal MF (1994) Cortical cytochrome oxidase activity is reduced in Alzheimer’s disease. J Neurochem 63: 2179–2184PubMedCrossRefGoogle Scholar
  108. Nordberg A (1997) Nicotinic receptors as new target for treatment of Alzheimer’s disease. Abstract, 41th Oholo Conference, EilatGoogle Scholar
  109. Ohkura T, Isse K, Akazawa K, Hamamoto M, Yaoi Y, Hagino N (1995) Long-term estrogen replacement therapy in female patients with dementia of the Alzheimer’s type: 7 case reports. Dementia 6: 99–107PubMedGoogle Scholar
  110. Olson L, Nordberg A, Von Holst H, Bäckman L, Ebendal T, Alafuzoff I, Amberla K,Hartvig P, Herlitz A, Lilja A, Lundquist H, Langström B, Meyerson B, Persson A, Viitanen M, Wimblad B, Seiger A (1992) Nerve growth factor affects 11C-nicotine binding, blood flow, EEG, and verbal episodic memory in an Alzheimer patient (case report). J Neural Transm [P-D Sect] 4: 79–95CrossRefGoogle Scholar
  111. Paganini-Hill A, Hendersen VW (1994) Estrogen deficiency and risk of Alzheimer’s disease. Am J Epidemiol 140: 256–261PubMedGoogle Scholar
  112. Palacios JM (1996) Alzheimer’s disease: new pharmacological perspectives. Meth Find Exp Clin Pharmacol 18 [Suppl B]: 67–68Google Scholar
  113. Parker W, Parks J, Filley C, Kleinschmidt-DeMasters B (1994) Electron transport chain defects in Alzheimer’s disease brain. Neurology 44: 1090–1096PubMedCrossRefGoogle Scholar
  114. Piovesan P, Pacifici L, Taglialatela G, Ramacci MT, Angelucci L (1994) ALCAR treatment increases choline acetyltransferase activity and NGF levels in the CNS of adult rats following fimbria fornix transection. Brain Res 633: 77–82PubMedCrossRefGoogle Scholar
  115. Rabin SJ, Mocchetti I (1995) GM1 ganglioside activates the high-affinity nerve growth factor receptor trkA. J Neurochem 65: 347–354PubMedCrossRefGoogle Scholar
  116. Reichmann H, Janetzky B (1997) Mitochondrialer Stoffwechsel bei Demenz vom Alzheimer Typ. In: Rösler M, Retz W, Thome J (Hrsg) Alzheimer Krankheit. Beltz, Weinheim, S 164–169Google Scholar
  117. Reichmann H, Flörke S, Hebenstreit G, Schrubar H, Riederer P (1993) Analyses of energy metabolism and mitochondrial genome in postmortem brain from patients with Alzheimer’s disease. J Neurol 240: 377–380PubMedCrossRefGoogle Scholar
  118. Rich J, Rasmusson D, Folstein M, Carson K, Brandt J (1995) Nonsteroidal antiinflammatory drugs in Alzheimer’s disease. Neurology 45: 51–55PubMedCrossRefGoogle Scholar
  119. Richard F, Helbecque N, Neuman E, Guez D, Levy R, Amouyel P (1997) APOE genotyping and response to drug treatment in Alzheimer’s disease. Lancet 349: 539PubMedCrossRefGoogle Scholar
  120. Riederer P, Sofic E, Moll G, Freyberger A, Wichart I, Gsell W, Jellinger K, Hebenstreit G, Youdim MBH (1990) Senile dementia of Alzheimer’s type and Parkinson’s disease: neurochemical overlaps and specific differences. In: Dostert P, Riederer P, Benedetti MS, Roncucci R (eds) Early markers in Parkinson’s and Alzheimer’s disease. Springer, Wien New York, pp 220–232Google Scholar
  121. Rogers J, Luber-Narod J, Styren S, Civin W (1988) Expression of immune system-associated antigen by cells of the human central nervous system. Relationship to the pathology of Alzheimer’s disease. Neurobiol Aging 9: 330–349Google Scholar
  122. Rogers J, Kirby L, Hempelman S, Berry D, McGeer P, Kazniak A, Zalinski J, Cofield M, Mansukhani L, Wilson P, Kogan F (1993) Clinical trial of indomethacin in Alzheimer’s disease. Neurology 43: 1609–1611PubMedCrossRefGoogle Scholar
  123. Rüther E, Ritter R, Apecechea M, Freytag S, Windisch M (1994) Efficacy of the peptidergic nootropic drug cerebrolysin in patients with senile dementia of the Alzheimer type (SDAT). Pharmacopsychiatry 27: 32–40PubMedCrossRefGoogle Scholar
  124. Sano M, Bell K, Cote L, Dooneief G, Lawton A, Legler L, Marder K, Naini A, Stern Y, Mayeux R (1992) Double-blind parallel design pilot study of acetyl-L-carnitine in patients with Alzheimer’s disease. Arch Neurol 49: 1137–1141PubMedCrossRefGoogle Scholar
  125. Schapira AHV, Reichmann H (1995) Electron transport chain defects in Alzheimer’s diease. Neurology 45: 599–600PubMedCrossRefGoogle Scholar
  126. Schneider LS, Farlow MK, Henderson VW, Pogoda JM (1996) Estrogen replacement therapy may enhance response to tacrine in women with Alzheimer’s disease. Neurology 45 [Suppl]: A288Google Scholar
  127. Schneider L, Farlow M, Henderson V, Pogoda J (1996) Effects of estrogen replacement therapy on response to tacrine in patients with Alzheimer’s disease. Neurology 46: 1580–1584PubMedCrossRefGoogle Scholar
  128. Scremin O, Li M, Scremin A, Jenden D (1997) Cholinesterase inhibition improves blood flow in the ischemic cerebral cortex. Brain Res Bull 42: 59–70PubMedCrossRefGoogle Scholar
  129. Shannon H, Bymaster F, Calligaro D, Greenwood B, Mitch C, Sawyer B, Ward J, Wong D, Olesen P, Sheardown M, Swedberg M, Suzdak P, Sauerberg P (1994) Xanomeline, a novel muscarinic receptor agonist with functional selectivity for ml receptors. J Pharmacol Exp Ther 269: 271–281PubMedGoogle Scholar
  130. Sinden J, Hodges H, Gray J (1995) Neural transplantation and recovery of cognitive function. Behav Brain Sci 18: 10–35CrossRefGoogle Scholar
  131. Smith MA, Sayre LM, Monnier VM, Perry G (1995) Radical ageing in Alzheimer’s disease. Trends Neurosci 18: 172–176PubMedCrossRefGoogle Scholar
  132. Snyder SH, Dawson TM (1995) Nitric oxide and related substances as neural messangers. In: Bloom FE, Kupfer DJ (eds) Psychopharmacology: the fourth generation of progress. Raven, New York, p 614Google Scholar
  133. Soncrent T, Raffaele K, Asthana S, Berardi A, Morris P, Haxby J (1993) Memory improvement without toxicity during chronic, low dose intravenous arecoline in Alzheimer’s disease. Psychopharmacology 112: 421–427CrossRefGoogle Scholar
  134. Spagnoli A, Lucca U, Menasce G, Bandera L, Cizza G, Forloni G, Tettamanti M, Frattura L, Tiraboschi P, Comelli M et al. (1991) Long-term acetyl-L-carnitine treatment in Alzheimer’s disease. Neurology 41: 1726–1732PubMedCrossRefGoogle Scholar
  135. Spiegel K, Callahan M, Emmerling M, Raby R, Schwarz R (1997) Multiple targets for the muscarinic agonist milameline in Alzheimer’s disease. Abstract, 41th Oholo Conference, EilatGoogle Scholar
  136. Sramek J, Block G, Reines S, Sawin S, Barchowsky A, Cutler N (1995a) A multiple-dose safety trial of eptastigmine in Alzheimer’s disease, with pharmacodynamic observations of red blood cell Cholinesterase. Life Sci 56: 319–326PubMedCrossRefGoogle Scholar
  137. Sramek J, Sedman A, Reece P, Hourani J, Bockbrader H, Cutler N (1995b) Safety and tolerability of CI-979 in patients with Alzheimer’s disease. Life Sci 57: 503–510PubMedCrossRefGoogle Scholar
  138. Sramek J, Hurley T, Wardle T, Satterwhite J, Hourani J, Dies F, Cutler N (1995C) The safety and tolerance of xanomeline tartrate in patients with Alzheimer’s disease. J Clin Pharmacol 35: 800–806PubMedGoogle Scholar
  139. Sramek J, Viereck C, Huff F, Wardle T, Hourani J, Stewart J, Cutler N (1995d) A „bridging“ (safety/tolerance) study of besipirdine hydrochloride in patients with Alzheimer’s disease. Life Sci 57: 1241–1248PubMedCrossRefGoogle Scholar
  140. Stewart W, Kawas C, Corrada M, Metter E (1997) Risk of Alzheimer’s disease and duration of NSAID use. Neurology 48: 626–632PubMedCrossRefGoogle Scholar
  141. Sudilovsky A, Cutler NR, Sramek JJ, Wardle T, Veroff AE, Mickelson W, Markowitz J, Repetti S (1993) A pilot clinical trial of angiotensin converting enzyme inhibitor ceranapril in Alzheimer disease. Alzheimer Dis Assoc Disord 7: 105–111PubMedCrossRefGoogle Scholar
  142. Svennerholm L (1994) Gangliosides — a new therapeutic agent against stroke and Alzheimer’s disease. Life Sci 55: 2125–2134PubMedCrossRefGoogle Scholar
  143. Svennerholm L, Gottfries C, Blennow, Fredman P, Karlsson I, Mansson J, Toffano G, Wallin A (1990) Parenteral administration of GM1 gan-glioside to presenile Alzheimer’s patients. Acta Neurol Scand 81: 45–53Google Scholar
  144. Tang M, Jacobs D, Stern Y, Marder K, Schofield P, Gurland B, Andrews H, Mayeux R (1996) Effect of oestrogen during menopause on risk and age at onset of Alzheimer’s disease. Lancet 348: 429–432PubMedCrossRefGoogle Scholar
  145. Tarriot P, Cohen R, Welkowitz J, Sunderland T, Newhouse P, Murphy D, Weingartner H (1988) Multiple-dose Arecoline infusions in Alzheimer’s disease. Arch Gen Psychiatry 45: 901–905CrossRefGoogle Scholar
  146. Thal L (1996) Neurotrophic factors. Prog Brain Res 109: 327–330PubMedCrossRefGoogle Scholar
  147. Thal L, Carta A, Clarke W, Ferris S, Friedland R, Petersen R, Pettegrew J, Pfeiffer E, Raskind M, Sano M, Tuszynski M, Woolson R (1996) A 1-year multicenter placebocontrolled study of acetyl-L-carnitine in patients with Alzheimer’s disease. Neurology 47: 705–711PubMedCrossRefGoogle Scholar
  148. Tooyama I, Kimura H, Cakiyama H, McGeer P (1990) Reactive microglia express class I and class II major histocompatibility complex antigens in Alzheimer disease. Brain Res 523: 273–280PubMedCrossRefGoogle Scholar
  149. Ved H, Koenig M, Dave J, Doctor B (1997) Huper-zine A, a potential therapeutic agent for dementia, reduces neuronal cell death caused by glutamate. Neuroreport 8: 963–968PubMedCrossRefGoogle Scholar
  150. Vrecko, K, Birkmayer JGD, Krainz J (1993) Stimulation of dopamine biosynthesis in cultured PC 12 phaeochromocytoma cells by the coenzyme nicotinamide adenindinucleotide (NADH). J Neural Transm [P-D Sect] 5:147–156CrossRefGoogle Scholar
  151. Warpman U, Nordberg A (1995) Epibatidine und ABT 418 reveal selective losses of α4β2 nicotinic receptors in Alzheimer brains. Neuro Report 6: 2419–2423Google Scholar
  152. Welner S, Dunnett S, Salamone J (1988) Transplantation of embryonic ventral forebrain grafts to the neocortex of rats with bilateral lesions of nucleus basalis magnocellularis ameliorates a lesion-induced deficit in spatial memory. Brain Res 463: 192–197PubMedCrossRefGoogle Scholar
  153. White HL, Scates PW (1990) Acetyl-L-carnitine as a precursor of acetylcholine. Neurochem Res 15: 597–601PubMedCrossRefGoogle Scholar
  154. Whitehouse P, Price D, Struble R, Clark A, Coyle J, DeLong M (1982) Alzheimer’s disease and senile dementia: loss of neurons in the basal forebrain. Science 215: 1237–1239PubMedCrossRefGoogle Scholar
  155. Wilson D, Satlin A, Inglis A, Everitt D, Zussman B, Boike S, Geregel I, Kumar R, Jurkasky D (1997) Cognitive efficacy of SB 202026 in rats and marmorsets at doses which do not induce side effects. Abstract, 41th Oholo Conference, EilatGoogle Scholar
  156. Winkler J, Ramirez G, Kuhn H, Peterson D, Daylollini P, Stewart G, Tuszynski M, Gage F, Thal L (1997) Reversible Schwann cell hyperplasia and sprouting of sensory and sympathetic neurites after intraventricular administration of nerve growth factor. Ann Neurol 41: 82–93PubMedCrossRefGoogle Scholar
  157. Xu S, Gao Z, Weng Z, Du Z, Xu W, Yang J, Zhang M, Tong Z, Fang Y, Chai X (1995) Efficacy of tablet huperzine-A on memory, cognition, and behavior in Alzheimer’s disease. Chung Kuo Yao Li Hsueh Pao 16: 391–395PubMedGoogle Scholar
  158. Yamamoto T, Hirano A (1985) Nucleus raphe dorsalis in Alzheimer’s disease: neurofibrillary tangles and loss of large neurons. Ann Neurol 17: 573–577PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Wien 1999

Authors and Affiliations

  • M. Rösler
  • A. Heidrich

There are no affiliations available

Personalised recommendations