Mitochondrial dysfunction and neuroinflammatory signaling in a humanized <i>APP</i> / <i>APOE</i> mouse model of Alzheimer's Disease risk

Our findings indicate consistent sex differences in neuroinflammatory and mitochondrial pathways in this mouse model. APOE genotype effects were evident in neuroinflammatory signatures, particularly in females. Specifically, elevated cGAS-STING signaling in female hAPP/hAPOE4s may drive a neuroinflammatory response, highlighting a potential role in increased AD risk for women during midlife aging. Together, these results highlight the importance of considering both biological sex and genotype effects when investigating the role of neuroinflammatory mechanisms and mitochondrial dysfunction in AD pathogenesis.