Sex-specific APOE4-dependent innate immunity regulates meningeal lymphatics, brain lipids, neuroinflammation, and cognition - PubMed
6 hours ago
- #APOE4
- #neuroinflammation
- #sexual dimorphism
- Sex and APOE4 interact to affect Alzheimer's disease risk, with sex-specific differences observed in immune activation and meningeal lymphatic function in APOE4/E4 mice compared to E3/E3 controls.
- APOE4 influences brain lipid composition and inflammation differently in females and males; these effects were partially reversed by CSF1R inhibition.
- Inhibiting innate immunity reduced neuroinflammation and improved cognition in female E4/E4 mice but worsened neuroinflammation and accelerated cognitive decline in male E4/E4 mice.
- APOE4 expression is linked to sexually dimorphic leukocyte activation profiles in the human brain, aligning with findings from the mouse model.
- The study underscores the need for personalized therapies targeting APOE, brain immunity, and meningeal lymphatics to support cognitive resilience in both sexes.