Fig. 6
Estrogen receptor β (ERβ) interacts with apolipoprotein E (ApoE) in the regulation of brain-derived neurotrophic factor (BDNF)–5-hydroxytryptamine 2A (5-HT2A) signaling and synaptic function in the female brain. The findings presented indicate that ApoE isoforms differentially modulate the BDNF–5-HT2A signaling and synaptic function in the female brain. Specifically, compared with ApoE2 and ApoE3, the presence of the ApoE4 allele exerts a largely negative impact on these signaling pathways, which predisposes the brain to an increased risk for depression, which further increases the risk for Alzheimer’s disease (AD). ERβ signaling positively modulates these brain pathways primarily in ApoE2 and ApoE3 brains, whereas it has a minimal role in the ApoE4 brain, implicating the potential interaction of ERβ signaling and ApoE isoforms in the modulation of certain functions in the female brain