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International Journal of Alzheimer’s Disease
Volume 2012, Article ID 489428, 9 pages
http://dx.doi.org/10.1155/2012/489428
Review Article

Apolipoprotein E: Essential Catalyst of the Alzheimer Amyloid Cascade

1Department of Molecular Medicine, Suncoast Gerontology Center, Johnnie B. Byrd Sr. Alzheimer’s Institute, University of South Florida, Tampa, FL 33620, USA
2Department of Neurology and Linda Crnic Institute for Downs Syndrome, School of Medicine, University of Colorado Aurora, CO 80045, USA
3Departments of Neurology, Pathology, and Psychiatry, New York University School of Medicine, New York, NY 10016, USA

Received 16 December 2011; Accepted 23 April 2012

Academic Editor: Laura Morelli

Copyright © 2012 Huntington Potter and Thomas Wisniewski. 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

The amyloid cascade hypothesis remains a robust model of AD neurodegeneration. However, amyloid deposits contain proteins besides Aβ, such as apolipoprotein E (apoE). Inheritance of the apoE4 allele is the strongest genetic risk factor for late-onset AD. However, there is no consensus on how different apoE isotypes contribute to AD pathogenesis. It has been hypothesized that apoE and apoE4 in particular is an amyloid catalyst or “pathological chaperone”. Alternatively it has been posited that apoE regulates Aβ clearance, with apoE4 been worse at this function compared to apoE3. These views seem fundamentally opposed. The former would indicate that removing apoE will reduce AD pathology, while the latter suggests increasing brain ApoE levels may be beneficial. Here we consider the scientific basis of these different models of apoE function and suggest that these seemingly opposing views can be reconciled. The optimal therapeutic target may be to inhibit the interaction of apoE with Aβ rather than altering apoE levels. Such an approach will not have detrimental effects on the many beneficial roles apoE plays in neurobiology. Furthermore, other Aβ binding proteins, including ACT and apo J can inhibit or promote Aβ oligomerization/polymerization depending on conditions and might be manipulated to effect AD treatment.