Introducing Human APOE into Aβ Transgenic Mouse Models

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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.
Funding Information
  • National Institute on Aging (P01AG03012801, ZEN-08-99900, UL1RR029879)
  • Alzheimer’s Association (P01AG03012801, ZEN-08-99900, UL1RR029879)
  • Center for Clinical and Translational Science (P01AG03012801, ZEN-08-99900, UL1RR029879)

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