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Introducing Human APOE into Aβ Transgenic Mouse Models

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Title: Introducing Human APOE into Aβ Transgenic Mouse Models
Author(s): Tai, Leon M.; Youmans, Katherine L.; Jungbauer, Lisa; Yu, Chunjiang; LaDu, Mary Jo
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.
Issue Date: 2011
Publisher: SAGE-Hindawi Access to Research
Citation Info: Tai LM, Youmans KL, Jungbauer L, Yu C, Ladu MJ. 2011. Introducing Human APOE into Aβ Transgenic Mouse Models. International Journal of Alzheimer's Disease, 2011:810981. doi:10.4061/2011/810981
Type: Article
Description: 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. doi:10.4061/2011/810981
ISSN: 2090-0252
Sponsor: Current LaDu lab funding includes NIH (NIA) P01AG03012801, Alzheimer’s Association ZEN-08-99900, UIC CCTS UL1RR029879.
Date Available in INDIGO: 2012-08-21

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