Translational potential of JAX humanized APOE mice: Peripheral interferon gamma induces systemic immuno‐metabolic dysfunction

Inflammation is a well‐documented feature of Alzheimer’s disease (AD) in human brain. Previous findings from our group demonstrated upregulated immune transcripts in the AD brain as well as sex differences in immune transcript levels during pre‐clinical midlife aging. Using our humanized APOE mouse model, we identified elevated immune transcripts in the female brain including interferon signaling genes, CD3, CD4, and MHCII. We hypothesized that activation via increased interferon gamma (IFN‐γ) during endocrine aging may disrupt the immune‐metabolic balance in the brain and therefore advance changes in grey and white matter. With this study, we test the hypothesis that increased levels of peripheral IFN‐γ induces genotype dependent immuno‐metabolic changes in the JAX humanized APOE (hAPOE) mouse model.