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International Journal of Alzheimer’s Disease
Volume 2012 (2012), Article ID 369808, 11 pages
http://dx.doi.org/10.1155/2012/369808
Review Article

Alzheimer's Disease and the Amyloid Cascade Hypothesis: A Critical Review

1Taub Institute for Research on Alzheimer's Disease and the Aging Brain, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA
2Gertrude H. Sergievsky Center, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA
3Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA

Received 28 November 2011; Accepted 3 January 2012

Academic Editor: Laura Morelli

Copyright © 2012 Christiane Reitz. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Since 1992, the amyloid cascade hypothesis has played the prominent role in explaining the etiology and pathogenesis of Alzheimer's disease (AD). It proposes that the deposition of β-amyloid (Aβ) is the initial pathological event in AD leading to the formation of senile plaques (SPs) and then to neurofibrillary tangles (NFTs), neuronal cell death, and ultimately dementia. While there is substantial evidence supporting the hypothesis, there are also limitations: (1) SP and NFT may develop independently, and (2) SPs and NFTs may be the products rather than the causes of neurodegeneration in AD. In addition, randomized clinical trials that tested drugs or antibodies targeting components of the amyloid pathway have been inconclusive. This paper provides a critical overview of the evidence for and against the amyloid cascade hypothesis in AD and provides suggestions for future directions.