The amyloid cascade hypothesis for Alzheimer's disease: an appraisal for the development of therapeutics

被引：1737

作者：

Karran, Eric ^{[1
]}

Mercken, Marc ^{[1
]}

De Strooper, Bart ^{[2
]}

机构：

[1] Janssen Res & Dev, Neurosci Therapeut Area, B-2340 Beerse, Belgium

[2] Katholieke Univ Leuven VIB, Dept Mol & Dev Genet, Louvain, Belgium

来源：

NATURE REVIEWS DRUG DISCOVERY | 2011年 / 10卷 / 09期

关键词：

GAMMA-SECRETASE INHIBITOR; GENOME-WIDE ASSOCIATION; CENTRAL-NERVOUS-SYSTEM; A-BETA; PRECURSOR PROTEIN; IN-VIVO; APOLIPOPROTEIN-E; MOUSE MODEL; PRESENILIN MUTATIONS; CLINICAL-TRIALS;

D O I：

10.1038/nrd3505

中图分类号：

Q81 [生物工程学（生物技术）]; Q93 [微生物学];

学科分类号：

071005 ; 0836 ; 090102 ; 100705 ;

摘要：

The amyloid cascade hypothesis, which posits that the deposition of the amyloid-beta peptide in the brain is a central event in Alzheimer's disease pathology, has dominated research for the past twenty years. Several therapeutics that were purported to reduce amyloid-beta production or aggregation have failed in Phase III clinical testing, and many others are in various stages of development. Therefore, it is timely to review the science underpinning the amyloid cascade hypothesis, consider what type of clinical trials will constitute a valid test of this hypothesis and explore whether amyloid-beta-directed therapeutics will provide the medicines that are urgently needed by society for treating this devastating disease.

引用

页码：698 / U1600

页数：15

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