APOE and sex: Key Players in Alzheimer’s Disease Pathology

Published on October 31, 2023

Just like how ingredients in a recipe can impact the final dish, the combination of age, APOE genotype, and sex have been found to influence the development of Alzheimer’s disease (AD) in EFAD transgenic mice. In this study, researchers observed the effects of these factors on amyloid beta (Aβ) pathology, neuroinflammation, and behavior in vivo. The results showed that female mice with the APOE4 genotype had the highest levels of Aβ deposition and neuroinflammation, leading to earlier behavioral deficits compared to other groups. Surprisingly, male mice with the APOE4 genotype had similar pathology levels to female mice with the APOE3 genotype. These findings suggest that having both the APOE4 genotype and being female increases the risk for AD. Moreover, as mice aged, being female seemed to have a similar impact on pathology as having the APOE4 genotype. Overall, this study highlights the importance of considering APOE genotype and sex as key players in AD pathology. To delve deeper into this fascinating research, check out the full article!

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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