Perspectives in clinical Alzheimer’s disease research and the development of antidementia drugs

  • M. Grundman
  • J. Corey-Bloom
  • L. J. Thal
Part of the Journal of Neural Transmission. Supplementa book series (NEURAL SUPPL, volume 53)


Current treatment approaches in Alzheimer’s disease are primarily symptomatic, with the major therapeutic strategy based on acetylcho-linesterase inhibition. Alzheimer’s disease research should advance over ensuing decade(s) to yield better symptomatic therapies, drugs designed to slow the rate of progression, and disease preventing agents. The next generation of cholinergic agents will include long acting cholinesterase inhibitors with a good safety profile and brain specific muscarinic agonists. The most critical advances in Alzheimer’s disease treatment, however, will target slowing of disease progression and prevention of dementia. Therapeutic agents are being developed that interfere with the synthesis, deposition and aggregation of β-amyloid protein. Clinical trials are presently being conducted with small molecules having nerve growth factor like activity (e.g. AIT-082, cerebrolysin). In addition, estrogen, anti-inflammatory agents (e.g. cyclo-oxygenase inhibitors) and antioxidant approaches (e.g. vitamin E) are currently being proposed or utilized in disease prevention trials.


Nerve Growth Factor Alzheimer Disease Cholinesterase Inhibitor Paired Helical Filament Paired Helical Filament 
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.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Adams JD, Jr, Klaidman LK, Odunze IN, et al (1991) Alzheimer’s and Parkinson’s disease. Brain levels of glutathione, glutathione disulfide, and vitamin E. Mol Chem Neuropathol 14: 213–226CrossRefGoogle Scholar
  2. Aisen PS (1997) Inflammation and Alzheimer’s disease: mechanisms and therapeutic strategies. Gerontology 43: 143–149PubMedCrossRefGoogle Scholar
  3. Aisen PS, Davis KL (1994) Inflammatory mechanisms in Alzheimer’s disease: implications for therapy. Am J Psychiatry 151: 1105–1113PubMedGoogle Scholar
  4. Akai F, Hiruma S, Sato T, et al (1992) Neurotrophic factor-like effect of FPF1070 on septal cholinergic neurons after transections of fimbria-fornix in the rat brain. Histol Histopathol 7: 213–221PubMedGoogle Scholar
  5. Albrecht E, Hingel S, Crailsheim K, et al (1993) The effects of Cerebrolysin on survival and sprouting of neurons from cerebral hemispheres and from the brain stem of chick embryos in vitro. In: Nicolini M, Zatta PF, Coraine B (eds) Alzheimer’s disease and related disorders. Pergamon Press, Oxford, pp 341–342Google Scholar
  6. Anand R, Harnan R, Gharabawi G (1997) Therapeutic effects of Exelon in the treatment of patients with Alzheimer’s disease. Neurology 48: A377Google Scholar
  7. Andersen K, Launer LJ, Ott A, et al (1995) Do nonsteroidal anti-inflammatory drugs decrease the risk for Alzheimer’s disease? The Rotterdam Study. Neurology 45: 1441–1445PubMedCrossRefGoogle Scholar
  8. Arneric SP, Sullivan JP, Decker MW, et al (1995) Potential treatment of Alzheimer disease using cholinergic channel activators (ChCAs) with cognitive enhancement, anxiolytic-like, and cytoprotective properties. Alzh Dis Assoc Disord 9 [Suppl 2]: 50–61CrossRefGoogle Scholar
  9. Balazs L, Leon M (1994) Evidence of an oxidative challenge in the Alzheimer’s brain. Neurochem Res 19: 1131–1137PubMedCrossRefGoogle Scholar
  10. Bartus RT, Dean RL, Flicker C (1987) Cholinergic psychopharmacology: an integration of human and animal research on memory. In: Meltzer HY (ed) Psychopharmacology: the third generation of progress. Raven Press, New York, pp 219–232Google Scholar
  11. Beal MF, Hyman BT, Koroshetz W (1993) Do defects in mitochondrial energy metabolism underlie the pathology of neurodegenerative diseases? Trends Neurosci 16: 125–131PubMedCrossRefGoogle Scholar
  12. Behl C, Davis J, Cole GM, et al (1992) Vitamin E protects nerve cells from amyloid beta protein toxicity. Biochem Biophys Res Commun 186: 944–950PubMedCrossRefGoogle Scholar
  13. Behl C, Davis JB, Lesley R, et al (1994) Hydrogen peroxide mediates amyloid beta protein toxicity. Cell 77: 817–827PubMedCrossRefGoogle Scholar
  14. Behl C, Widmann M, Trapp T, et al (1995) 17-beta estradiol protects neurons from oxidative stress-induced cell death in vitro. Biochem Biophys Res Commun 216: 473–482PubMedCrossRefGoogle Scholar
  15. Bodick NC, Offen WW, Levey AI, et al (1997) Effects of xanomeline, a selective muscarinic receptor agonist, on cognitive function and behavioral symptoms in Alzheimer disease. Arch Neurol 54: 465–473PubMedCrossRefGoogle Scholar
  16. Breitner JC, Gau BA, Welsh KA, et al (1994) Inverse association of anti-inflammatory treatments and Alzheimer’s disease: initial results of a co-twin control study. Neurology 44: 227–232PubMedCrossRefGoogle Scholar
  17. Breitner JC, Welsh KA, Helms MJ, et al (1995) Delayed onset of Alzheimer’s disease with nonsteroidal anti-inflammatory and histamine H2 blocking drugs. Neurobiol Aging 16: 523–530PubMedCrossRefGoogle Scholar
  18. Brugge K, Katzman R, Hill LR, et al (1992) Serological alpha 1-antichymotrypsin in Down’s syndrome and Alzheimer’s disease. Ann Neurol 32: 193–197PubMedCrossRefGoogle Scholar
  19. Bruno V, Battaglia G, Copani A, et al (1994) Protective action of idebenone against excitotoxic degeneration in cultured cortical neurons. Neurosci Lett 178: 193–196PubMedCrossRefGoogle Scholar
  20. Buccafusco JJ, Jackson WJ, Terry AV, Jr, et al (1995) Improvement in performance of a delayed matching-to-sample task by monkeys following ABT-418: a novel cholinergic channel activator for memory enhancement. Psychopharmacology 120: 256–266PubMedCrossRefGoogle Scholar
  21. Butterfield DA, Hensley K, Harris M, et al (1994) beta-Amyloid peptide free radical fragments initiate synaptosomal lipoperoxidation in a sequence-specific fashion: implications to Alzheimer’s disease. Biochem Biophys Res Commun 200: 710–715PubMedCrossRefGoogle Scholar
  22. Caldwell BM (1954) An evaluation of psychological effects of sex hormone administration in aged women. J Gerontol 9: 168–174PubMedCrossRefGoogle Scholar
  23. Campbell JE, Sullivan JP, Arnold W, et al (1996) Pharmacokinetic and safety studies on ABT-089; an orally active cholinergic channel modulator. Soc Neurosci 22: 1264Google Scholar
  24. Chen L, Richardson JS, Caldwell JE, et al (1994) Regional brain activity of free radical defense enzymes in autopsy samples from patients with Alzheimer’s disease and from nondemented controls. Int J Neurosci 75: 83–90PubMedCrossRefGoogle Scholar
  25. Connor JR, Snyder BS, Beard JL, et al (1992) Regional distribution of iron and iron-regulatory proteins in the brain in aging and Alzheimer’s disease. J Neurosci Res 31: 327–335PubMedCrossRefGoogle Scholar
  26. Copani A, Bruno V, Battaglia G, et al (1995) Activation of metabotropic glutamate receptors protects cultured neurons against apoptosis induced by beta-amyloid peptide. Mol Pharmacol 47: 890–897PubMedGoogle Scholar
  27. Cummings J, Beiber F, Mas J, et al (1997) Metrifonate in Alzheimer’s disease: results of a dose-finding study. In: Iqbal K, Winblad B, Nishimura T, et al (eds) Alzheimer’s disease: biology, diagnosis and therapeutics. Wiley, Chichester, pp 665–669Google Scholar
  28. Davies P, Maloney AJ (1976) Selective loss of central cholinergic neurons in Alzheimer’s disease. Lancet ii: 1403CrossRefGoogle Scholar
  29. Davis RE, Doyle PD, Carroll RT, et al (1995) Cholinergic therapies for Alzheimer’s disease. Palliative or disease altering? Arzneimittelforschung 45: 425–431PubMedGoogle Scholar
  30. Decker MW, Curzon P, Brioni JD, et al (1994) Effects of ABT-418, a novel cholinergic channel ligand, on place learning in septal-lesioned rats. Eur J Pharmacol 261: 217–222PubMedCrossRefGoogle Scholar
  31. Decker MW, Bannon AW, Curzon P, et al (1996) Effects of ABT-089, a novel cholinergic channel modulator, on cognitive performance in rats and monkeys. Soc Neurosci 22: 1263Google Scholar
  32. Donnelly-Roberts DL, Xue IC, Arneric SP, et al (1996) In vitro neuroprotective properties of the novel cholinergic channel activator (ChCA), ABT-418. Brain Res 719: 36–44PubMedCrossRefGoogle Scholar
  33. Dorje F, Levey AI, Brann MR (1991) Immunological detection of muscarinic receptor subtype proteins (m1–m5) in rabbit peripheral tissues. Mol Pharmacol 40: 459–462PubMedGoogle Scholar
  34. Fisher A, Heldman E, Gurwitz D, et al (1996) Ml agonists for the treatment of Alzheimer’s disease. Novel properties and clinical update. Ann NY Acad Sci 777: 189–196PubMedCrossRefGoogle Scholar
  35. Fuji K, Hiramatsu M, Kameyama T, et al (1993) Effects of repeated administration of propentofylline on memory impairment produced by basal forebrain lesion in rats. Eur J Pharmacol 236: 411–417PubMedCrossRefGoogle Scholar
  36. Furuta A, Price DL, Pardo CA, et al (1995) Localization of Superoxide dismutases in Alzheimer’s disease and Down’s syndrome neocortex and hippocampus. Am J Pathol 146: 357–367PubMedGoogle Scholar
  37. Gage FH, Armstrong DM, Williams LR, et al (1988) Morphological response of axotomized septal neurons to nerve growth factor. J Comp Neurol 269: 147–155PubMedCrossRefGoogle Scholar
  38. Glasky AJ, Kirat R, Middlemiss PJ, et al (1995) A novel purine derivative AIT-082 increases the synthesis of NGF, FGF-2 and NT-3 mRNA in astrocytes. Soc Neurosci Abstr 21: 295Google Scholar
  39. Glasky AJ, Melchior CL, Pirzadeh B, et al (1994) Effect of AIT-082, a purine analog, on working memory in normal and aged mice. Pharmacol Biochem Behav 47: 325–329PubMedCrossRefGoogle Scholar
  40. Glasky AJ, Ritzmann RF, Rathbone MP, et al (1996) Neurotrophins, growth factors and mimetic agents as neuroprotectors in the treatment of Alzheimer’s disease. In: Becker R, Giacobini E (eds) Alzheimer disease: from molecular biology to therapy. Birkhäuser, Boston, pp 119–124Google Scholar
  41. Good PF, Perl DP, Bierer LM, et al (1992) Selective accumulation of aluminum and iron in the neurofibrillary tangles of Alzheimer’s disease: a laser microprobe (LAMMA) study. Ann Neurol 31: 286–292PubMedCrossRefGoogle Scholar
  42. Good PF, Werner P, Hsu A, et al (1996) Evidence of neuronal oxidative damage in Alzheimer’s disease. Am J Pathol 149: 21–28PubMedGoogle Scholar
  43. Goodman Y, Mattson MP (1994) Staurosporine and K-252 compounds protect hippocampal neurons against amyloid beta-peptide toxicity and oxidative injury. Brain Res 650: 170–174PubMedCrossRefGoogle Scholar
  44. Grundke-Iqbal I, Fleming J, Tung YC, et al (1990) Ferritin is a component of the neuritic (senile) plaque in Alzheimer dementia. Acta Neuropathol 81: 105–110PubMedCrossRefGoogle Scholar
  45. Gupta-Bansal R, Frederickson RC, Brunden KR (1995) Proteoglycan-mediated inhibition of A beta proteolysis. A potential cause of senile plaque accumulation. J Biol Chem 270: 18666–18671PubMedCrossRefGoogle Scholar
  46. Gurwitz D, Haring R, Pinkas-Kramarski R, et al (1995) NGF-dependent neurotrophic-like effects of AF102B, an Ml muscarinic agonist, in PC12M1 cells. Neuroreport 6: 485–488PubMedCrossRefGoogle Scholar
  47. Haass C, Hung AY, Schlossmacher MG, et al (1993) beta-Amyloid peptide and a 3-kDa fragment are derived by distinct cellular mechanisms. J Biol Chem 268: 3021–3024PubMedGoogle Scholar
  48. Hall ED, Andrus PK, Smith SL, et al (1997) Pyrrolopyrimidines: novel brain-penetrating antioxidants with neuroprotective activity in brain injury and ischemia models. J Pharmacol Exp Ther 281: 895–904PubMedGoogle Scholar
  49. Harris KA, Oyler GA, Doolittle GM, et al (1993) Okadaic acid induces hyperphosphorylated forms of tau protein in human brain slices. Ann Neurol 33: 77–87PubMedCrossRefGoogle Scholar
  50. Hensley K, Carney JM, Mattson MP, et al (1994) A model for beta-amyloid aggregation and neurotoxicity based on free radical generation by the peptide: relevance to Alzheimer disease. Proc Natl Acad Sci USA 91: 3270–3274PubMedCrossRefGoogle Scholar
  51. Hensley K, Aksenova M, Carney JM, et al (1995) Amyloid beta-peptide spin trapping. I: Peptide enzyme toxicity is related to free radical spin trap reactivity. Neuroreport 6: 489–492PubMedCrossRefGoogle Scholar
  52. Higaki J, Quon D, Zhong Z, et al (1995) Inhibition of beta-amyloid formation identifies proteolytic precursors and subcellular site of catabolism. Neuron 14: 651–659PubMedCrossRefGoogle Scholar
  53. Higgins GA, Mufson EJ (1989) NGF receptor gene expression is decreased in the nucleus basalis in Alzheimer’s disease. Exp Neurol 106: 222–236PubMedCrossRefGoogle Scholar
  54. Hirai K, Hayako H, Kato K, et al (1996) Idebenone protects against oxidative stress mediated neuronal cell death by coupling with the mitochondrial electron transport system. Soc Neurosci 22: 200Google Scholar
  55. Honjo H, Ogino Y, Naitoh K, et al (1989) In vivo effects by estrone sulfate on the central nervous system-senile dementia (Alzheimer’s type). J Steroid Biochem 34: 521–525PubMedCrossRefGoogle Scholar
  56. Jackson CV, Holland AJ, Williams CA, et al (1988) Vitamin E and Alzheimer’s disease in subjects with Down’s syndrome. J Ment Defic Res 32: 479–484PubMedGoogle Scholar
  57. Jeandel C, Nicolas MB, Dubois F, et al (1989) Lipid peroxidation and free radical scavengers in Alzheimer’s disease. Gerontology 35: 275–282PubMedCrossRefGoogle Scholar
  58. Jenkinson ML, Bliss MR, Brain AT, et al (1989) Rheumatoid arthritis and senile dementia of the Alzheimer’s type [letter]. Br J Rheumatol 28: 86–88PubMedCrossRefGoogle Scholar
  59. Jones GM, Sahakian BJ, Levy R, et al (1992) Effects of acute subcutaneous nicotine on attention, information processing and short-term memory in Alzheimer’s disease. Psychopharmacology 108: 485–494PubMedCrossRefGoogle Scholar
  60. Jonhagen M, Wahlund LO, Amberla K, et al (1996) Nerve growth factors as a treatment of Alzheimer’s disease. Neurobiol Aging 17Google Scholar
  61. Kantor HI, Michael CM, Shore H (1973) Estrogen for older women. Am J Obstet Gynecol 116: 115–118PubMedGoogle Scholar
  62. Kihara T, Shimohama S, Sawada H, et al (1997) Nicotinic receptor stimulation protects neurons against beta-amyloid toxicity. Ann Neurol 42: 159–163PubMedCrossRefGoogle Scholar
  63. Kisilevsky R, Lemieux LJ, Fraser PE, et al (1995) Arresting amyloidosis in vivo using small-molecule anionic sulphonates or sulphates: implications for Alzheimer’s disease. Nat Med 1: 143–148PubMedCrossRefGoogle Scholar
  64. Knapp MJ, Knopman DS, Solomon PR, et al (1994) A 30-week randomized controlled trial of high-dose tacrine in patients with Alzheimer’s disease. The Tacrine Study Group. JAMA 271: 985–991Google Scholar
  65. Knopman D, Schneider L, Davis K, et al (1996) Long-term tacrine (Cognex) treatment: effects on nursing home placement and mortality, Tacrine Study Group. Neurology 47: 166–177PubMedCrossRefGoogle Scholar
  66. Knops J, Suomensaari S, Lee M, et al (1995) Cell-type and amyloid precursor protein-type specific inhibition of A beta release by bafilomycin Al, a selective inhibitor of vacuolar ATPases. J Biol Chem 270: 2419–2422PubMedCrossRefGoogle Scholar
  67. Kosik KS (1990) Tau protein and Alzheimer’s disease. Curr Opin Cell Biol 2: 101–104PubMedCrossRefGoogle Scholar
  68. Kumar R, Orgogozo J (1997) Efficacy and safety of SB 202026 as a symptomatic treatment for Alzheimer’s disease. In: Iqbal K, Winblad B, Nishimura T, et al (eds) Alzheimer’s disease: biology, diagnosis and therapeutics. Wiley, Chichester, pp 677–685Google Scholar
  69. Lakis J, Glasco S, Miller SW, et al (1995) Production of reactive oxygen species correlates with decreased cytochrome oxidase activity in Alzheimer’s disease cybrids. Soc Neurosci Abstr 21: 979Google Scholar
  70. Lazarovici P, Rasouly D, Friedman L, et al (1996) K252a and staurosporine microbial alkaloid toxins as prototype of neurotropic drugs. Adv Exp Med Biol 391: 367–377PubMedCrossRefGoogle Scholar
  71. Ledesma MD, Bonay P, Colaco C, et al (1994) Analysis of microtubule-associated protein tau glycation in paired helical filaments. J Biol Chem 269: 21614–21679PubMedGoogle Scholar
  72. Lee PN (1994) Smoking and Alzheimer’s disease: a review of the epidemiological evidence. Neuroepidemiology 13: 131–144PubMedCrossRefGoogle Scholar
  73. Levey AI, Kitt CA, Simonds WF, et al (1991) Identification and localization of muscarinic acetylcholine receptor proteins in brain with subtype-specific antibodies. J Neurosci 11: 3218–3226PubMedGoogle Scholar
  74. Lorenzo A, Yankner BA (1994) Beta-amyloid neurotoxicity requires fibril formation and is inhibited by congo red. Proc Natl Acad Sci USA 91: 12243–12247PubMedCrossRefGoogle Scholar
  75. Ma J, Yee A, Brewer HB, Jr, et al (1994) Amyloid-associated proteins alpha 1-antichymotrypsin and apolipoprotein E promote assembly of Alzheimer beta-protein into filaments. Nature 372: 92–94PubMedCrossRefGoogle Scholar
  76. Ma J, Brewer HB, Jr, Potter H (1996) Alzheimer A beta neurotoxicity: promotion by antichymotrypsin, ApoE4; inhibition by A beta-related peptides. Neurobiol Aging 17: 773–780PubMedCrossRefGoogle Scholar
  77. Masferrer JL, Zweifel BS, Manning PT, et al (1994) Selective inhibition of inducible cyclooxygenase 2 in vivo is antiinfiammatory and nonulcerogenic. Proc Natl Acad Sci USA 91: 3228–3232PubMedCrossRefGoogle Scholar
  78. Matsubara E, Hirai S, Amari M, et al (1990) Alpha 1-antichymotrypsin as a possible biochemical marker for Alzheimer-type dementia. Ann Neurol 28: 561–567PubMedCrossRefGoogle Scholar
  79. McEwen BS, Alves SE, Bulloch K, et al (1997) Ovarian steroids and the brain: implications for cognition and aging. Neurology 48: S 8–15CrossRefGoogle Scholar
  80. McGeer PL, McGeer EG (1995) The inflammatory response system of brain: implications for therapy of Alzheimer and other neurodegenerative diseases. Brain Res Brain Res Rev 21: 195–218PubMedCrossRefGoogle Scholar
  81. McGeer PL, McGeer E, Rogers J, et al (1990) Anti-inflammatory drugs and Alzheimer disease [letter]. Lancet 335: 1037PubMedCrossRefGoogle Scholar
  82. Mecocci P, MacGarvey U, Beal MF (1994) Oxidative damage to mitochondrial DNA is increased in Alzheimer’s disease. Ann Neurol 36: 747–751PubMedCrossRefGoogle Scholar
  83. Seibert K, Zhang Y, Leahy K, et al (1994) Pharmacological and biochemical demonstration of the role of cyclooxygenase 2 in inflammation and pain. Proc Natl Acad Sci USA 91: 12013–12017PubMedCrossRefGoogle Scholar
  84. Simmons LK, May PC, Tomaselli KJ, et al (1994) Secondary structure of amyloid beta peptide correlates with neurotoxic activity in vitro. Mol Pharmacol 45: 373–379PubMedGoogle Scholar
  85. Smith MA, Kutty RK, Richey PL, et al (1994) Heme oxygenase-1 is associated with the neurofibrillary pathology of Alzheimer’s disease. Am J Pathol 145: 42–47PubMedGoogle Scholar
  86. Smith MA, Rudnicka-Nawrot M, Richey PL, et al (1995) Carbonyl-related posttranslational modification of neurofilament protein in the neurofibrillary pathology of Alzheimer’s disease. J Neurochem 64: 2660–2666PubMedCrossRefGoogle Scholar
  87. Sramek JJ, Anand R, Wardle TS, et al (1996) Safety/tolerability trial of SDZ ENA 713 in patients with probable Alzheimer’s disease. Life Sci 58: 1201–1207PubMedCrossRefGoogle Scholar
  88. Stewart WF, Kawas C, Corrada M, et al (1997) Risk of Alzheimer’s disease and duration of NSAID use. Neurology 48: 626–632PubMedCrossRefGoogle Scholar
  89. Strada O, Hirsch EC, Javoy-Agid F, et al (1992) Does loss of nerve growth factor receptors precede loss of cholinergic neurons in Alzheimer’s disease? An autoradio-graphic study in the human striatum and basal forebrain. J Neurosci 12: 4766–4774PubMedGoogle Scholar
  90. Strittmatter WJ, Saunders AM, Schmechel D, et al (1993) Apolipoprotein E: high-avidity binding to beta-amyloid and increased frequency of type 4 allele in late-onset familial Alzheimer disease. Proc Natl Acad Sci USA 90: 1977–1981PubMedCrossRefGoogle Scholar
  91. Sullivan JP, Anderson DJ, Briggs CA, et al (1996) ABT-089: A potent and selective cholinergic channel modulator with neuroprotective properties. Soc Neurosci Abstr 22: 1263Google Scholar
  92. Tang MX, Jacobs D, Stern Y, et al (1996) Effect of estrogen during menopause on risk and age at onset of Alzheimer’s disease. Lancet 348: 429–432PubMedCrossRefGoogle Scholar
  93. Tennent GA, Lovat LB, Pepys MB (1995) Serum amyloid P component prevents proteolysis of the amyloid fibrils of Alzheimer disease and systemic amyloidosis. Proc Natl Acad Sci USA 92: 4299–4303PubMedCrossRefGoogle Scholar
  94. Thal LJ, Fuld PA, Masur DM, et al (1983) Oral physostigmine and lecithin improve memory in Alzheimer disease. Ann Neurol 13: 491–496PubMedCrossRefGoogle Scholar
  95. Thal LJ, Schwartz G, Sano M, et al (1996) A multicenter double-blind study of controlled-release physostigmine for the treatment of symptoms secondary to Alzheimer’s disease. Physostigmine Study Group. Neurology 47: 1389–1395Google Scholar
  96. Thomas T, Thomas G, McLendon C, et al (1996) beta-Amyloid-mediated vasoactivity and vascular endothelial damage. Nature 380: 168–171PubMedCrossRefGoogle Scholar
  97. Tocco G, Freire-Moar J, Schreiber SS, et al (1997) Maturational regulation and regional induction of cyclooxygenase-2 in rat brain: implications for Alzheimer’s disease. Exp Neurol 144: 339–349PubMedCrossRefGoogle Scholar
  98. Tomiyama T, Shoji A, Kataoka K, et al (1996) Inhibition of amyloid beta protein aggregation and neurotoxicity by rifampicin. Its possible function as a hydroxyl radical scavenger. J Biol Chem 271: 6839–6844PubMedCrossRefGoogle Scholar
  99. Troetel WM, Imbimbo BP (1997) Overview of the development of epatstigmine, a long-acting cholinesterase inhibitor. In: Iqbal K, Winblad B, Nishimura T, et al (eds) Alzheimer’s disease: biology, diagnosis and therapeutics. Wiley, Chichester, pp 671–676Google Scholar
  100. Tojanowski JQ, Lee VM (1995) Phosphorylation of paired helical filament tau in Alzheimer’s disease neurofibrillary lesions: focusing on phosphatases. FASEB J 9: 1570–1576Google Scholar
  101. Vane J (1994) Towards a better aspirin [news; comment]. Nature 367: 215–216PubMedCrossRefGoogle Scholar
  102. Vitek MP, Bhattacharya K, Glendening JM, et al (1994) Advanced glycation end products contribute to amyloidosis in Alzheimer disease. Proc Natl Acad Sci USA 91: 4766–4770PubMedCrossRefGoogle Scholar
  103. Webster S, Glabe C, Rogers J (1995) Multivalent binding of complement protein C1Q to the amyloid beta-peptide (A beta) promotes the nucleation phase of A beta aggregation. Biochem Biophys Res Commun 217: 869–875PubMedCrossRefGoogle Scholar
  104. Whitehouse PJ, Price DL, Clark AW, et al (1981) Alzheimer disease: evidence for selective loss of cholinergic neurons in the nucleus basalis. Ann Neurol 10: 122–126PubMedCrossRefGoogle Scholar
  105. Wieland E, Schutz E, Armstrong VW, et al (1995) Idebenone protects hepatic microsomes against oxygen radical-mediated damage in organ preservation solutions. Transplantation 60: 444–451PubMedCrossRefGoogle Scholar
  106. Wilcock G, Wilkinson D (1997) Galanthamine hydrobromide: interim results of a group comparative, placebo-controlled study of efficacy and safety in patients with a diagnosis of senile dementia of the Alzheimer type. In: Iqbal K, Winblad B, Nishimura T, et al (eds) Alzheimer’s disease: biology, diagnosis and therapeutics. Wiley, Chichester, pp 661–664Google Scholar
  107. Winkler J, Ramirez GA, Kuhn HG, et al (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
  108. Xu SS, Gao ZX, Weng Z, et al (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
  109. Yamagata K, Andreasson KI, Kaufmann WE, et al (1993) Expression of a mitogeninducible cyclooxygenase in brain neurons: regulation by synaptic activity and glucocorticoids. Neuron 11: 371–386PubMedCrossRefGoogle Scholar
  110. Yan SD, Chen X, Schmidt AM, et al (1994) Glycated tau protein in Alzheimer disease: a mechanism for induction of oxidant stress. Proc Natl Acad Sci USA 91: 7787–7791PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Wien 1998

Authors and Affiliations

  • M. Grundman
    • 1
  • J. Corey-Bloom
    • 1
  • L. J. Thal
    • 1
  1. 1.Department of NeurosciencesUniversity of CaliforniaSan DiegoUSA

Personalised recommendations