Implications of amyloid precursor protein and subsequent β-amyloid production to the pharmacotherapy of Alzheimer's disease

Pharmacotherapy

Volumn 22, Issue 12 I, 2002, Pages 1547-1563

  Rojas Fernandez, Carlos H ^a   Chen, Ming ^b   Fernandez, Hugo L ^b  

^a TEXAS TECH UNIVERSITY HEALTH SCIENCES CENTER   (United States)

^b Bay Pines VA Medical Center   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

2,2 DICHLOROVINYLMETHYLPHOSPHATE; ALPHA AMINO 3 HYDROXY 5 METHYL 4 ISOXAZOLEPROPIONIC ACID; ALPHA SECRETASE; ALZHEIMER DISEASE VACCINE; AMYLOID BETA PROTEIN; AMYLOID PRECURSOR PROTEIN; BETA SECRETASE; CARBACHOL; CHOLINESTERASE INHIBITOR; ENZYME ACTIVATOR; ENZYME INHIBITOR; ESTROGEN; GAMMA SECRETASE; GLUTAMIC ACID; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE INHIBITOR; KAINIC ACID; METHYL BETA CYCLODEXTRIN; MEVINOLIN; MUSCARINIC M1 RECEPTOR AGONIST; NERVE GROWTH FACTOR; NICOTINE; PHENSERINE; PHORBOL ESTER; PHYSOSTIGMINE; PRAVASTATIN; SIMVASTATIN; TALSACLIDINE; UNCLASSIFIED DRUG; UNINDEXED DRUG; VASOPRESSIN; XANOMELINE;

AGING; ALZHEIMER DISEASE; CAREGIVER; CENTRAL NERVOUS SYSTEM; CLINICAL TRIAL; DEMENTIA; DISEASE COURSE; DRUG TARGETING; FAMILY; HEALTH CARE SYSTEM; HUMAN; IMMUNIZATION; IMMUNOTHERAPY; INFLAMMATION; NERVE DEGENERATION; NEUROPATHOLOGY; NEUROTOXICITY; NONHUMAN; PATHOLOGY; PREVALENCE; PROTEIN PROCESSING; PROTEIN SYNTHESIS; REVIEW; RISK FACTOR;

EID: 0036894091     PISSN: 02770008     EISSN: None     Source Type: Journal    
DOI: 10.1592/phco.22.17.1547.34116     Document Type: Review

References (138)

1. Cummings JL, Khachaturian ZS. Definitions and diagnostic criteria. In: Gauthier S, ed. Clinical Diagnosis and Management of Alzheimer's Disease, 2nd Ed. London: Martin Dunitz, 2001:3-13.
2. Bouchard RW, Rossorm MN. Typical clinical features. In: Gauthier S, ed. Clinical Diagnosis and Management of Alzheimer's Disease, 2nd Ed. London: Martin Dunitz, 2001:57-72.
3. Zabar Y, Kawas CH. Epidemiology and clinical genetics of Alzheimer's disease. In: Clark CM, Trojanowski JQ, eds. Neurodegenerative Dementias: Clinical Features and Pathological Mechanisms. New York: McGraw-Hill, 2000:79-94.
4. Bachman DL, Wolf PA, Linn RT, et al. Incidence of dementia and probable Alzheimer's disease in a general population: The Framingham study. Neurology 1993;43:515-19.
5. Jorm AF, Korten AE, Henderson AS. The prevalence of dementia: A quantitative integration of the literature. Acta Psychiatr Scand 1987;76:465-79.
6. Evans DA, Funkenstein HH, Albert MS, et al. Prevalence of Alzheimer's disease in a community of older persons. JAMA 1989;262:2251-6.
7. Wolfson C, Wolfson DB, Asgharian M, et al. A reevaluation of the duration of survival after the onset of dementia. N Engl J Med 2001;344:1111-16.
8. Haley WE. The family caregiver's role in Alzheimer's disease. Neurology 1997;48(suppl 6):S25-9.
9. Ernst RL, Hay JW. Economic research on Alzheimer disease: A review of the literature. Alzheimer Dis Assoc Disord 1997;11(suppl 6):135-45.
10. Alzheimer A. Uber eine eigenartige erkangkung der hirninde. Allgemeine Zeitschr Psychiatr Psychisch-Gerichtliche Meidzin 1907;64:146-8. (English translation in Arch Neurol 1969;21:109-10.)
11. Blass JP. Alzheimer's disease and Alzheimer's dementia: Distinct but overlapping entities. Neurobiol Aging, in press.
12. Chen M, Fernandez HL. Alzheimer movement re-examined 25 years later: Is it a "disease" or a senile condition in medical nature? Front Biosci 2001;6:e30-40.
13. Blumenthal HT. A view of the aging-disease relationship from age 85. J Gerontol A Biol Sci Med Sci 1999;54:B255-9.
14. Terry RD, Katzman R. Life span and synapses: Will there be a primary senile dementia? Neurobiol Aging 2001;22:347-8.
15. Price JL, McKeel DW, Morris JC. Synaptic loss and pathological change in older adults: Aging versus disease? Neurobiol Aging 2001;22:351-2.
16. Emmerling MR, Gracon S, Roher AE. Towards a unifying hypothesis of Alzheimer's disease pathogenesis and pathophysiology In: Gauthier S, ed. Clinical Diagnosis and Management of Alzheimer's Disease, 2nd Ed. London: Martin Dunitz, 2001:33-56.
17. Mayeux R, Ottman R, Maestre G, et al. Synergistic effect of traumatic head injury and apolipoprotein E4 in patients with Alzheimer's disease. Neurology 1995;45:555-7.
18. Skoog I, Kalaria RN, Bretler MM. Vascular factors and Alzheimer's disease. Alzheimer Dis Assoc Disord 1999;13(suppl 3):S106-14.
19. Bowler JV, Steenhuis R, Hachinski V. Conceptual background to vascular cognitive impairment. Alzheimer Dis Assoc Disord 1999;13(suppl 3):S30-7.
20. Dickson DW. Neuropathological diagnosis of Alzheimer's disease: A perspective from longitudinal clinicopathological studies. Neurobiol Aging 1997;18:S21-6.
21. Dickson DW. The pathogenesis of senile plaques. J Neuropathol Exp Neurol 1997;56:321-39.
22. Yamaguchi H, Hirai S, Morimatsu M, et al. A variety of cerebral amyloid deposits in the brains of the Alzheimer-type dementia demonstrated by β protein immunostaining. Acta Neuropathol 1988;76:541-9.
23. Yamaguchi H, Nakazato, Hirai S, et al. Electron micrograph of diffuse plaques: Initial stage of senile plaque formation in the Alzheimer brain. Am J Pathol 1989;135:593-7.
24. Selkoe DJ. Translating cell biology into therapeutic advances in Alzheimer's disease. Nature 1999;399(suppl 6738):A23-31.
25. Funato H, Yoshimura M, Kusui K, et al. Quantitation of amyloid β-protein (Aβ) in the cortex during aging and Alzheimer's disease. Am J Pathol 1998;152:1633-40.
26. Masliah E, Licastro F. Neuronal and synaptic loss, reactive gliosis, microglial response, and induction of the complement cascade in Alzheimer's disease. In: Clark CM, Trojanowski JQ, eds. Neurodegenerative Dementias: Clinical Features and Pathological Mechanisms. New York: McGraw-Hill, 2000:131-46.
27. Hardy JA, Higgins GA. Alzheimer's disease: The amyloid cascade hypothesis. Science 1992;256:184-5.
28. Bishop GM, Robinson SR. The amyloid hypothesis: Let sleeping dogmas lie? Neurobiol Aging, in press.
29. Neve RL, Robakis NK. Alzheimer's disease: A re-examination of the amyloid hypothesis. Trends Neurosci 1998;21:15-19.
30. Perry G, Nunomura A, Raina AK, Smith MA. Amyloid junkies [letter]. Lancet 2000;355:757.
31. Selkoe DJ. Alzheimer's disease: Genes, proteins, and therapy. Physiol Rev 2001;81:741-66.
32. Coulson EJ, Paliga K, Beyreuther K, Masters CL. What the evolution of the amyloid protein precursor supergene family tells us about its function. Neurochem Int 2000;36:174-84.
33. Bayer TA, Wirths O, Majtenyl K, et al. Key factors in Alzheimer's disease: β-Amyloid precursor protein processing, metabolism and intraneuronal transport. Brain Pathol 2001;11:1-11.
34. Dodart JC, Mathis C, Ungerer A. The β-amyloid precursor protein and its derivatives: From biology to learning and memory processes. Rev Neurosci 2000;11:75-93.
35. DeStrooper B, Annaert W. Proteolytic processing and cell biological functions of the amyloid precursor protein. J Cell Sci 2000;113:1857-70.
36. Sinha S, Lieberburg I. Cellular mechanisms of β-amyloid production and secretion. Proc Nat Acad Sci USA 1999;96:11049-53.
37. Arriagada PV, Growdon JH, Hedley-Whyte T, Hyman BT. Neurofibrillary tangles, but not senile plaques parallel duration and severity of Alzheimer's disease. Neurology 1992;42:631-9.
38. Roses AD. Apolipoprotein E affects the rate of Alzheimer disease expression: β-Amyloid burden is a secondary consequence dependent on ApoE genotype and duration of disease. J Neuropathol Exp Neurol 1994;53:429-37.
39. Cumming BJ, Cotman CW. Image analysis of β-amyloid load in Alzheimer's disease and relation to dementia severity. Lancet 1995;346:1524-8.
40. Morris JC, Storandt M, McKeel DW, et al. Cerebral amyloid deposition and diffuse plaques in "normal" aging: Evidence for presymptomatic and very mild Alzheimer's disease. Neurology 1996;46:707-19.
41. McLean CA, Cherny RA, Fraser FW, et al. Soluble pool of Aβ amyloid as a determinant of severity of neurodegeneration in Alzheimer's disease. Ann Neurol 1999;46:860-6.
42. Cummings BJ, Pike CJ, Shankle R, Cotman CW. β-Amyloid deposition and other measures of neuropathology predict cognitive status in Alzheimer's disease. Neurobiol Aging 1996;17:921-33.
43. Kanne SM, Balota DA, Storandt M, McKeel DW, Morris JC. Relating anatomy to function in Alzheimer's disease: Neuropsychological profiles predict regional neuropathology 5 years later. Neurology 1998;50:979-85.
44. Haroutunian V, Perl DP, Dushyant P, et al. Regional distribution of neuritic plaques in the nondemented elderly and subjects with Alzheimer's disease. Arch Neurol 1998;55:1185-91.
45. Naslund J, Haroutunian V, Mohs R, Davis KL, Greengard P, Buxbaum JD. Correlation between elevated levels of amyloid β-peptide in the brain and cognitive decline. JAMA 2000;283:1571-7.
46. Klein WL, Krafft GA, Finch CE. Targeting small Aβ oligomers: The solution to an Alzheimer's disease conundrum? Trends Neurosci 2001;24:219-24.
47. Klein WL. ADDLs and protofibrils: The missing links? Neurobiol Aging 2002;23:231-3.
48. Lue LF, Kuo YM, Roher AE, et al. Soluble amyloid β peptide concentration as a predictor of synaptic change in Alzheimer's disease. Am J Pathol 1999;155:853-62.
49. Tucker HM, Estus S. Evolution and the scientific method. Neurobiol Aging, in press.
50. Dominguez DI, DeStrooper B, Annaert W. Secretases as therapeutic targets for the treatment of Alzheimer's disease. Amyloid 2001;8:124-42.
51. Vassar R, Citron M. Aβ-generating enzymes: Recent advances in β- and γ-secretase research. Neuron 2000;27:419-22.
52. Howlett DR, Simmons DL, Dingwall C, Christie G. In search of an enzyme: The β-secretase of Alzheimer's disease is an aspartic proteinase. Trends Neurosci 2000;23:565-70.
53. Selkoe DJ, Wolfe MS. In search of γ-secretase: Presenilin at the cutting edge. Proc Nat Acad Sci USA 2000;97:5690-2.
54. Chen M, Fernandez HL. Where do Alzheimer's plaques and tangles come from? Aging induced protein degradation inefficiency Front Biosci 2001;6:e1-11.
55. Guenette SY, Tanzi RE. Progress toward valid transgenic mouse models for Alzheimer's disease. Neurobiol Aging 1999;20:201-11.
56. Schenk D, Barbour R, Dunn W, et al. Immunization with amyloid-β attenuates Alzheimer-disease-like pathology in the PDAPP mouse. Nature 1999;400:173-7.
57. Weiner HL, Lemere CA, Maron R, et al. Nasal administration of amyloid-β peptide decreases cerebral amyloid burden in a mouse model of Alzheimer's disease. Ann Neurol 2000;48:567-79.
58. Janus C, Pearson J, McLaurin J, et al. Aβ peptide immunization reduces behavioural impairment and plaques in a model of Alzheimer's disease. Nature 2000;408:979-82.
59. Morgan D, Diamond DM, Gottschall PE, et al. Aβ peptide vaccination prevents memory loss in an animal model of Alzheimer's disease. Nature 2000;408:982-5.
60. Dodart JC, Bales KR, Gannon KS, et al. Immunization reverses memory deficits without reducing brain Aβ burden in Alzheimer's disease model. Nature 2002;5:452-7.
61. Bruce-Keller AJ, Estus S. Concern over the amyloid vaccine: Amyloid heterogeneity and Fc receptor signaling. Neurobiol Aging, in press.
62. Eastwood R. The vanishing plaque [editorial]. Int Psychogeriatr 2001;13:3.
63. Forstl H. AN-1792: A frank revolution [editorial]? Int Psychogeriatr 2001;13:3-4.
64. Check E. Nerve inflammation halts trial for Alzheimer's drug [letter]. Nature 2002;415:462.
65. Pasinetti GM, Ho L, Pompl P. Amyloid immunization in Alzheimer's disease: Do we promote amyloid scavenging at the cost of inflammatory degeneration? Neurobiol Aging, in press.
66. Das P, Golde TE. Open peer commentary regarding Aβ immunization and CNS inflammation by Passitnetti et al. Neurobiol Aging, in press.
67. Itzhaki RF, Wozniak MA, Dobson CB. Inflammatory consequences: Benevolent, or virulent? Neurobiol Aging, in press.
68. Schenk DB, Yednock T. The role of microglia in Alzheimer's disease: friend or foe? Neurobiol Aging 2002, in press.
69. Bowers WJ, Federoff HJ. Amyloid immunotherapy-engendered CNS inflammation. Neurobiol Aging 2002, in press.
70. Hardy J. Testing times for the "amyloid" cascade hypothesis". Neurobiol Aging, in press.
71. Vassar R, Bennett BD, Babu-Khan S, et al. β-secretase cleavage of Alzheimer's amyloid protein precursor protein by the transmembrane aspartic protease BACE. Science 1999;286:735-41.
72. Hussain I, Powell DJ, Howlett DR, et al. ASP1 (BACE2) cleaves the amyloid precursor protein at the β-secretase site. Mol Cell Neurosci 2000;16:609-19.
73. Lin X, Koelsch G, Wu S, Downs D, Dashti A, Tang J. Human aspartic protease memapsin 2 cleaves the β-secretase site of β-amyloid precursor protein. Proc Natl Acad Sci USA 2000;97:1456-60.
74. Sinha S, Anderson JP, Barbour R, et al. Purification and cloning of amyloid precursor protein β-secretase from human brain. Nature 1999;402:537-40.
75. Yan R, Blenkowski MJ, Schuck ME, et al. Membrane-anchored aspartyl protease with Alzheimer's disease β-secretase activity. Nature 1999;402:533-7.
76. Farzan M, Schnitlzer N, Leung D, Choe H. BACE2, a β- secretase homolog, cleaves at the β site and within the amyloid-β region of the amyloid-β precursor protein. Proc Nat Acad Sci USA 2000;97:9712-17.
77. Haas C, DeStrooper B. The presenilins in Alzheimer's disease: Proteolysis holds the key Science 1999;286:916-19.
78. Artavanis-Tsakonas S, Rand MR, Lake RJ. Notch signaling: Cell fate control and signal integration in development. Science 1999;284:770-6.
79. Struhl G, Adachi A. Nuclear access and action of Notch in vivo. Cell 1998;93:649-60.
80. Hadland BK, Manley NR, Su D, et al. γ-secretase inhibitors repress thymocyte development. Proc Nat Acad Sci USA 2001;98:7487-91.
81. Schroeter EH, Kisslinger JA, Kopan R. Notch-1 signalling requires ligand-induced proteolytic release of intracellular domain. Nature 1998;393:382-6.
82. Herreman A, Hartmann D, Annaert W, et al. Presenilin 2 deficiency causes a mild pulmonary phenotype and no changes in amyloid precursor protein processing but enhances the embryonic lethal phenotype of presenilin 1 deficiency. Proc Natl Acad Sci USA 1999;96:11872-7.
83. Lichtenthaler SF, Wang R, Grimm H, Ulion SN, Masters CL, Beyreuther K. Mechanism of the cleavage identified by phenylalanine-scanning mutagenesis of the transmembrane domain of the amyloid precursor protein. Proc Nat Acad Sci USA 1999;96:3053-8.
84. Dovey J, John V, Anderson JP, et al. Functional γ-secretase inhibitors reduce β-amyloid peptide levels in the brain. J Neurochem 2001;76:173-81.
85. Yamada K, Nabeshima T. Animal models of Alzheimer's disease and evaluation of anti-dementia drugs. Pharmacol Ther 2000;88:93-113.
86. Nunan J, Small DH. Regulation of APP cleavage by α-, β-, and γ-secretases. FEBS Lett 2000;483:6-10.
87. Kojima S, Omori M. Two-way cleavage of β-amyloid protein precursor by multicatalytic proteinase. FEBS Lett 1992; 304:57-60.
88. Miyazaki K, Hasegawa M, Funahashi K, Umeda M. A metalloproteinase inhibitor domain in Alzheimer amyloid protein precursor. Nature 1993;362:839-41.
89. Roberts SB, Ripellino JA, Ingalls KM, Robakis NK, Felsentein KM. Non-amyloidogenic cleavage of the β-amyloid precursor protein by an integral membrane metalloendopeptidase. J Biol Chem 1994;269:3111-16.
90. Marambaud P, Rieunier F, Wilk S, Martinez J, Checler F. Contribution of the proteasome to the α-secretase pathway in Alzheimer's disease. Adv Exp Med Biol 1997;421:267-72.
91. Zhang W, Espinoza D, Hines V, Innis M, Mehta P, Miller DL. Characterization of β-amyloid peptide precursor processing by the yeast Yap3 and Mkc7 proteases. Biochim Biophys Acta 1997;1359:110-22.
92. Komano H, Seeger M, Gandy S, Wang GT, Krafft GA, Fuller RS. Involvement of cell surface glycosyl-phosphatidylinositol- linked aspartyl proteases in α-secretase-type cleavage and ectodomain solubilization of human Alzheimer β-amyloid precursor protein in yeast. J Biol Chem 1998;273:31648-51.
93. Buxbaum JD, Liu KN, Slack JL, et al. Evidence that tumor necrosis factor-α-converting enzyme is involved in regulated α-secretase cleavage of the Alzheimer amyloid protein precursor. J Biol Chem 1998;273:27765-7.
94. Fahrenholz F, Gilbert S, Kojro E, Lammich S, Postina R. α-secretase activity of the disintegrin metalloprotease ADAM 10: Influences of domain structure. Ann N Y Acad Sci 2000;920:215-22.
95. Chen M, Durr J, Fernandez HL. Possible role of calpain in normal processing of β-amyloid precursor protein in human platelets. Biochem Biophys Res Commun 2000;273:170-5.
96. Nitsch RM, Slack BE, Wurtman RJ, Growdon JH. Release of Alzheimer amyloid precursor derivatives stimulated by activation of muscarinic acetylcholine receptors. Science 1992;258:304-7.
97. Nitsch RM, Deng A, Wurtman RJ, Growdon JH. Metabotropic glutamate receptor subtype mGLuR1α stimulates the secretion of the amyloid β-protein precursor ectodomain. J Neurochem 1997;69:704-12.
98. Nitsch RM, Deng M, Tennis M, Schoenfeld D, Growdon JH. The selective muscarinic M1 agonist AF102B decreases levels of total Aβ in cerebrospinal fluid of patients with Alzheimer's disease. Ann Neurol 2000;48:913-18.
99. Hung AY, Haas C, Nitsch RM, et al. Activation of protein kinase C inhibits cellular production of the amyloid β-protein. J Biol Chem 1993;268:22959-62.
100. Eckols K, Bymaster FP, Mitch CH, Shannon HE, Ward JS, DeLapp NW. The muscarinic M1 agonist xanomeline increases soluble amyloid precursor protein release from Chinese hamster ovary-m1 cells. Life Sci 1995;57:1183-90.
101. Wolf BA, Wertkin AM, Jolly YC, et al. Muscarinic regulation of Alzheimer's disease amyloid precursor protein secretion and amyloid β protein production in human neuronal NT2N cells. J Biol Chem 1995;270:4916-22.
102. Muller DM, Medla K, Farber SA, Nitsch RM. Muscarinic M1 receptor agonists increase the secretion of the amyloid precursor protein ectodomain. Life Sci 1996;60:985-91.
103. Haring R, Fisher A, Marciano D, et al. Mitogen-activated protein kinase-dependent and protein kinase C-dependent pathways link the m1 muscarinic receptor to β-amyloid precursor protein secretion. J Neurochem 1998;71:2094-103.
104. Lin L, Georgievska B, Mattson A, Isacson O. Cognitive changes and modified processing of amyloid precursor protein in the cortical and hippocampal system after cholinergic synapse loss and muscarinic receptor activation. Proc Nat Acad Sci USA 1999;96:12108-13.
105. Beach TG, Walker DG, Potter PE, Sue LI, Fisher A. Reduction of cerebrospinal fluid amyloid β after systemic administration of M1 muscarinic agonists. Brain Res 2001;905:220-3.
106. Chen M, Fernandez HL. The Alzheimer's plaques, tangles and memory deficits may have a common deficit. IV. Can calpain act as α-secretase? Front Biosci 1998;3:A66-75.
107. Wolozin B, Kellman, Ruosseau P, Celesia GG, Siegel G. Decreased prevalence of Alzheimer disease associated with 3- hydroxy-3-methylglutaryl coenzyme A reductase inhibitors. Arch Neurol 2000;57:1439-43.
108. Jick H, Zornberg GL, Jick SS, Drachman DA. Statins and the risk of dementia. Lancet 2000;356:1627-31.
109. Rockwood K, Kirkland S, Hogan DB, et al. Use of lipid lowering agents, indication bias, and the risk of dementia in community dwelling elderly people. Arch Neurol 2002;59: 223-7.
110. Yaffe K, Barrett-Connor E, Lin F, Grady D. Serum lipoprotein levels, statin use, and cognitive function in older women. Arch Neurol 2002;59:378-84.
111. Simons M, Keller P, DeStrooper B, Beyreuther K, Dotti CG, Simons K. Cholesterol depletion inhibits the generation of β-amyloid in hippocampal neurons. Proc Nat Acad Sci USA 1998;95:6460-4.
112. 40 in vitro and in vivo. Proc Nat Acad Sci USA 2001;98:5856-61.
113. Kojro E, Gimpl G, Lammich S, Marz W, Fahrenholz F. Low cholesterol stimulates the nonamyloidogenic pathway by its effect on the α-secretase ADAM 10. Proc Nat Acad Sci USA 2001;98:5815-20.
114. Locatelli S, Lutjohann D, Schmidt HHJ, Otto C, Beisiegel U, von Bergmann K. Reduction of plasma 24s-hydroxy-cholesterol (cerebrosterol) levels using high-dosage simvastatin in patients with hypercholesterolemia: Evidence that simvastatin affects cholesterol metabolism in the human brain. Arch Neurol 2002;59:214-16.
115. Simons M, Keller P, Dichgans J, Schulz JB. Cholesterol and Alzheimer's disease: Is there a link? Neurology 2001;57: 1089-93.
116. Mori F, Lai CC, Fusi F, Giacobini E. Cholinesterase inhibitors increase secretion of APPs in rat brain cortex. Neuroreport 1995;6:633-6.
117. Lahiri DK, Farlow MR. Differential effect of tacrine and physostigmine on the secretion of the β-amyloid precursor protein in cell lines. J Mol Neurosci 1996;7:41-9.
118. Lahiri DK, Farlow MR, Sambamurti K. The secretion of amyloid β-peptides is inhibited in the tacrine-treated human neuroblastoma cells. Brain Res Mol Brain Res 1998;62:131-40.
119. Lahiri DK, Farlow MR, Hintz N, Utsuki T, Greig NH. Cholinesterase inhibitors, β-amyloid precursor protein and amyloid β-peptides in Alzheimer's disease. Acta Neurol Scand 2000;176(suppl):60-7.
120. Haroutunian V, Greig N, Pei XF, et al. Pharmacological modulation of Alzheimer's β-amyloid precursor protein levels in the CSF of rats with forebrain cholinergic system lesions. Brain Res Mol Brain Res 1997;46:161-8.
121. Borroni B, Colciaghi F, Pastorino L, et al. Amyloid precursor protein in platelets of patients with Alzheimer disease: Effect of acetylcholinesterase inhibitor treatment. Arch Neurol 2001;58:442-6.
122. Levin ED, Simon BB. Nicotinic acetylcholine involvement in cognitive function in animals. Psychopharmacology 1998;138:217-30.
123. Newhouse PA, Potter A, Levin ED. Nicotinic system involvement in Alzheimer's and Parkinson's disease. Drugs Aging 1997;11:206-28.
124. Court J, Martin-Ruiz C, Piggott M, Spurden D, Griffiths M, Perry E. Nicotinic receptor abnormalities in Alzheimer's disease. Biol Psychiatry 2001;49:175-84.
125. Zamani MR, Allen YS, Owen GP, Gray JA. Nicotine modulates the neurotoxic effect of β-amyloid protein(25-35) in hippocampal cultures. Neuroreport 1997;8:513-17.
126. Kihara T, Shimohama S, Sawada H, et al. Nicotinic receptor stimulation protects neurons against β-amyloid toxicity. Ann Neurol 1997;42:159-63.
127. Kihara T, Shimohama S, Urushitani M, et al. Stimulation of α4β2 nicotinic acetylcholine receptors inhibits β-amyloid toxicity. Brain Res 1998;792:331-4.
128. Svensson AL, Nordberg A. Tacrine and donepezil attenuate the neurotoxic effect of Aβ(25-35) in rat PC12 cells. Neuroreport 1998;9:1519-22.
129. Giacobini E. Cholinesterase inhibitors stabilize Alzheimer's disease. Ann N Y Acad Sci 2000;920:321-7.
130. Fernandez HL, Ross GS, Nadelhaft I. Neurogenic calcitonin gene-related peptide: A neurotrophic factor in the maintenance of acetylcholinesterase molecular forms in adult skeletal muscles. Brain Res 1999;844:83-97.
131. Bush AI, Tanzi RE. The galvanization of β-amyloid in Alzheimer's disease. Proc Nat Acad Sci USA 2002;99:7317-19.
132. Cherny RA, Atwood CS, Xilinas ME, et al. Treatment with a copper-zinc chelator markedly and rapidly inhibits β-amyloid accumulation in Alzheimer's disease transgenic mice. Neuron 2001;30:665-76.
133. Alzheimer Research Forum. Bad News is Official: The Rofecoxib and Naproxen Clinical Trial Has Failed. Available from http://www.alzforum.org/new/detail.asp?id=623. Accessed August 20, 2002.
134. De Strooper B, Konig G. An inflammatory drug prospect. Nature 2001;414:159-60.
135. Davies P. A very incomplete comprehensive theory of Alzheimer's disease. Ann N Y Acad Sci 2000;924:8-16.
136. Churchill JD, Galvez R, Colcombe S, Swain RA, Kramer AF, Greenough WT. Exercise, experience and the aging brain. Neurobiol Aging 2002;5691:1-15.
137. Wilson RS, Mendes de Leon CF, Barnes LL, et al. Participation in cognitively stimulating activities and risk of incident Alzheimer disease. JAMA 2002;287:742-8.
138. Laurin D, Verreault R, Lindsay J, MacPherson K, Rockwood K. Physical activity and risk of cognitive impairment and dementia in elderly persons. Arch Neurol 2001;58:498-504.