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International Journal of Alzheimer’s Disease
Volume 2011, Article ID 134971, 12 pages
Review Article

Impacts of Membrane Biophysics in Alzheimer's Disease: From Amyloid Precursor Protein Processing to Aβ Peptide-Induced Membrane Changes

Department of Biological Engineering, University of Missouri, Columbia, MO 65211, USA

Received 27 October 2010; Revised 30 December 2010; Accepted 21 January 2011

Academic Editor: Katsuhiko Yanagisawa

Copyright © 2011 Sholpan Askarova et al. 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.


An increasing amount of evidence supports the notion that cytotoxic effects of amyloid-β peptide (Aβ), the main constituent of senile plaques in Alzheimer's disease (AD), are strongly associated with its ability to interact with membranes of neurons and other cerebral cells. Aβ is derived from amyloidogenic cleavage of amyloid precursor protein (AβPP) by β- and γ-secretase. In the nonamyloidogenic pathway, AβPP is cleaved by α-secretases. These two pathways compete with each other, and enhancing the non-amyloidogenic pathway has been suggested as a potential pharmacological approach for the treatment of AD. Since AβPP, α-, β-, and γ-secretases are membrane-associated proteins, AβPP processing and Aβ production can be affected by the membrane composition and properties. There is evidence that membrane composition and properties, in turn, play a critical role in Aβ cytotoxicity associated with its conformational changes and aggregation into oligomers and fibrils. Understanding the mechanisms leading to changes in a membrane's biophysical properties and how they affect AβPP processing and Aβ toxicity should prove to provide new therapeutic strategies for prevention and treatment of AD.