Androgens Protect Against Apolipoprotein E4-Induced Cognitive Deficits

The study found that apolipoprotein E4 (apoE4) increased the risk of Alzheimer's disease (AD) and impaired spatial learning and memory, particularly in female mice. Androgen treatment improved memory deficits in female apoE4 mice but had no effect on female apoE3 mice. Male apoE4 mice developed memory deficits after androgen receptor (AR) blockade, unlike male apoE3 mice. Untreated apoE4 mice had lower cytosolic AR levels in the neocortex compared to other groups. Androgen treatment increased AR levels and improved memory in female apoE4 mice, suggesting that apoE4-induced cognitive decline could be mitigated by stimulating AR-dependent pathways.