The amyloid hypothesis for Alzheimer's disease: a critical reappraisal

被引：631

作者：

Hardy, John ^{[1
,2
]}

机构：

[1] UCL, Inst Neurol, Reta Lilla Weston Inst, London, England

[2] UCL, Inst Neurol, Dept Mol Neurosci, London, England

来源：

JOURNAL OF NEUROCHEMISTRY | 2009年 / 110卷 / 04期

基金：

英国医学研究理事会;

关键词：

Alzheimer's disease; amyloid; congophilic angiopathy; dementia; pathogenesis; tau; BETA IMMUNIZATION AN1792; LONG-TERM POTENTIATION; A-BETA; MOUSE MODEL; IN-VIVO; APOLIPOPROTEIN-E; NEUROFIBRILLARY TANGLES; MISSENSE MUTATIONS; PRECURSOR PROTEIN; CANDIDATE GENE;

D O I：

10.1111/j.1471-4159.2009.06181.x

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The amyloid hypothesis has been the basis for most work on the pathogenesis of Alzheimer's disease. Recent clinical trials based on this hypothesis have been inconclusive. In this article I review the current status of the hypothesis and suggest that a major scientific need is to understand the normal function of amyloid-beta precursor protein (APP) and think how this may relate to the cell death in the disease process.

引用

页码：1129 / 1134

页数：6

共 75 条

[1]

Atwood CS, 2003, SCIENCE, V299, P1014

[2] Amyloid-β:: A vascular sealant that protects against hemorrhage? [J].

Atwood, CS ;

Bishop, GM ;

Perry, G ;

Smith, MA .

JOURNAL OF NEUROSCIENCE RESEARCH, 2002, 70 (03) :356-356

[3] Lack of apolipoprotein E dramatically reduces amyloid beta-peptide deposition [J].

Bales, KR ;

Verina, T ;

Dodel, RC ;

Du, YS ;

Altstiel, L ;

Bender, M ;

Hyslop, P ;

Johnstone, EM ;

Little, SP ;

Cummins, DJ ;

Piccardo, P ;

Ghetti, B ;

Paul, SM .

NATURE GENETICS, 1997, 17 (03) :263-264

[4] Peripherally administered antibodies against amyloid β-peptide enter the central nervous system and reduce pathology in a mouse model of Alzheimer disease [J].

Bard, F ;

Cannon, C ;

Barbour, R ;

Burke, RL ;

Games, D ;

Grajeda, H ;

Guido, T ;

Hu, K ;

Huang, JP ;

Johnson-Wood, K ;

Khan, K ;

Kholodenko, D ;

Lee, M ;

Lieberburg, I ;

Motter, R ;

Nguyen, M ;

Soriano, F ;

Vasquez, N ;

Weiss, K ;

Welch, B ;

Seubert, P ;

Schenk, D ;

Yednock, T .

NATURE MEDICINE, 2000, 6 (08) :916-919

[5] Familial Alzheimer's disease-linked presenilin 1 variants elevate A beta 1-42/1-40 ratio in vitro and in vivo [J].

Borchelt, DR ;

Thinakaran, G ;

Eckman, CB ;

Lee, MK ;

Davenport, F ;

Ratovitsky, T ;

Prada, CM ;

Kim, G ;

Seekins, S ;

Yager, D ;

Slunt, HH ;

Wang, R ;

Seeger, M ;

Levey, AI ;

Gandy, SE ;

Copeland, NG ;

Jenkins, NA ;

Price, DL ;

Younkin, SG .

NEURON, 1996, 17 (05) :1005-1013

[6] NEUROPATHOLOGICAL STAGING OF ALZHEIMER-RELATED CHANGES [J].

BRAAK, H ;

BRAAK, E .

ACTA NEUROPATHOLOGICA, 1991, 82 (04) :239-259

[7] A high-density whole-genome association study reveals that APOE is the major susceptibility gene for sporadic late-onset Alzheimer's disease [J].

Coon, Keith D. ;

Myers, Amanda J. ;

Craig, David W. ;

Webster, Jennifer A. ;

Pearson, John V. ;

Lince, Diane Hu ;

Zismann, Victoria L. ;

Beach, Thomas G. ;

Leung, Doris ;

Bryden, Leslie ;

Halperin, Rebecca F. ;

Marlowe, Lauren ;

Kaleem, Mona ;

Walker, Douglas G. ;

Ravid, Rivka ;

Heward, Christopher B. ;

Rogers, Joseph ;

Papassotiropoulos, Andreas ;

Reiman, Eric M. ;

Hardy, John ;

Stephan, Dietrich A. .

JOURNAL OF CLINICAL PSYCHIATRY, 2007, 68 (04) :613-618

[8] Microvascular pathology in the aging human brain:: Evidence that senile plaques are sites of microhaemorrhages [J].

Cullen, Karen M. ;

Kocsi, Zoltan ;

Stone, Jonathan .

NEUROBIOLOGY OF AGING, 2006, 27 (12) :1786-1796

[9] A QUANTITATIVE MORPHOMETRIC ANALYSIS OF THE NEURONAL AND SYNAPTIC CONTENT OF THE FRONTAL AND TEMPORAL CORTEX IN PATIENTS WITH ALZHEIMERS-DISEASE [J].

DAVIES, CA ;

MANN, DMA ;

SUMPTER, PQ ;

YATES, PO .

JOURNAL OF THE NEUROLOGICAL SCIENCES, 1987, 78 (02) :151-164

[10] A presenilin-1-dependent γ-secretase-like protease mediates release of Notch intracellular domain [J].

De Strooper, B ;

Annaert, W ;

Cupers, P ;

Saftig, P ;

Craessaerts, K ;

Mumm, JS ;

Schroeter, EH ;

Schrijvers, V ;

Wolfe, MS ;

Ray, WJ ;

Goate, A ;

Kopan, R .

NATURE, 1999, 398 (6727) :518-522

← 1 2 3 4 5 6 7 8 →