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Delivanoglou et al. show that expression of APOE4, a risk factor for Alzheimer’s disease, leads to sexually dimorphic lymphatic and inflammatory responses in mice and humans alike. Suppressing APOE4-induced innate immunity had contrasting effects on cognition in females and males, highlighting the need for immunotherapies tailored to each sex.
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Sex-specific APOE4-dependent innate immunity regulates meningeal lymphatics, brain lipids, neuroinflammation, and cognition