EFAD transgenic mice as a human APOE relevant preclinical model of Alzheimer's disease.
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ABSTRACT:
SUBMITTER: Tai LM
PROVIDER: S-EPMC5580905 | biostudies-literature | 2017 Sep
REPOSITORIES: biostudies-literature
Publications
EFAD transgenic mice as a human <i>APOE</i> relevant preclinical model of Alzheimer's disease.
Tai Leon M LM Balu Deebika D Avila-Munoz Evangelina E Abdullah Laila L Thomas Riya R Collins Nicole N Valencia-Olvera Ana Carolina AC LaDu Mary Jo MJ
Journal of lipid research 20170407 9
Identified in 1993, <i>APOE4</i> is the greatest genetic risk factor for sporadic Alzheimer's disease (AD), increasing risk up to 15-fold compared with <i>APOE3</i>, with <i>APOE2</i> decreasing AD risk. However, the functional effects of <i>APOE4</i> on AD pathology remain unclear and, in some cases, controversial. In vivo progress to understand how the human (h)-<i>APOE</i> genotypes affect AD pathology has been limited by the lack of a tractable familial AD-transgenic (FAD-Tg) mouse model exp ...[more]
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Project description:Increasing evidence supports that age, APOE and sex interact to modulate Alzheimer's disease (AD) risk, however the underlying pathways are unclear. One way that AD risk factors may modulate cognition is by impacting amyloid beta (Aβ) accumulation as plaques, and/or neuroinflammation Therefore, the goal of the present study was to evaluate the extent to which age, APOE and sex modulate Aβ pathology, neuroinflammation and behavior in vivo. To achieve this goal, we utilized the EFAD mice, which express human APOE3 or APOE4 and have five familial AD mutations (FAD) that result in Aβ42 overproduction. We assessed Aβ levels, reactive glia and Morris water maze performance in 6-, 10-, 14-, and 18-month-old EFAD mice. Female APOE4 mice had the highest Aβ deposition, fibrillar amyloid deposits and neuroinflammation as well as earlier behavior deficits. Interestingly, we found that female APOE3 mice and male APOE4 mice had similar levels of pathology. Collectively our data support that the combination of APOE4 and female sex is the most detrimental combination for AD, and that at older ages, female sex may be equivalent to APOE4 genotype.
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