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International Journal of Alzheimer’s Disease
Volume 2011, Article ID 810981, 9 pages
http://dx.doi.org/10.4061/2011/810981
Review Article

Introducing Human APOE into Aβ Transgenic Mouse Models

1Department of Anatomy and Cell Biology, University of Illinois at Chicago, Chicago, IL 60612, USA
2Translational Neurobiology, Medtronic Incorporated, Minneapolis, MN 55432, USA

Received 21 July 2011; Accepted 15 August 2011

Academic Editor: Patrizia Mecocci

Copyright © 2011 Leon M. Tai 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.

Abstract

Apolipoprotein E (apoE) and apoE/amyloid-β (Aβ) transgenic (Tg) mouse models are critical to understanding apoE-isoform effects on Alzheimer's disease risk. Compared to wild type, apoE/ mice exhibit neuronal deficits, similar to apoE4-Tg compared to apoE3-Tg mice, providing a model for Aβ-independent apoE effects on neurodegeneration. To determine the effects of apoE on Aβ-induced neuropathology, apoE/ mice were crossed with Aβ-Tg mice, resulting in a significant delay in plaque deposition. Surprisingly, crossing human-apoE-Tg mice with apoE//Aβ-Tg mice further delayed plaque deposition, which eventually developed in apoE4/Aβ-Tg mice prior to apoE3/Aβ-Tg. One approach to address hAPOE-induced temporal delay in Aβ pathology is an additional insult, like head injury. Another is crossing human-apoE-Tg mice with Aβ-Tg mice that have rapid-onset Aβ pathology. For example, because 5xFAD mice develop plaques by 2 months, the prediction is that human-apoE/5xFAD-Tg mice develop plaques around 6 months and 12 months before other human-apoE/Aβ-Tg mice. Thus, tractable models for human-apoE/Aβ-Tg mice continue to evolve.