APOE genotype and sex modulate Alzheimer's disease pathology in aged EFAD transgenic mice

Increasing evidence supports that age, 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, and sex modulate Aβ pathology, neuroinflammation and behavior . To achieve this goal, we utilized the EFAD mice, which express human or 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 mice had the highest Aβ deposition, fibrillar amyloid deposits and neuroinflammation as well as earlier behavior deficits. Interestingly, we found that female mice and male mice had similar levels of pathology. Collectively our data support that the combination of and female sex is the most detrimental combination for AD, and that at older ages, female sex may be equivalent to genotype.