Associations between brain inflammatory profiles and human neuropathology are altered based on apolipoprotein E ε4 genotype

We examined the pathological relationships between microglia, associated cytokines, and AD pathologies within the dorsolateral frontal cortex in a community-based aging cohort of 154 participants from the Framingham Heart Study. Associations between inflammatory markers and AD pathologies were significantly altered by the presence of the APOE ε4 allele. In APOE ε4 positive participants, IL-4, IL-10, and IFN-γ were associated with increased levels of Aβ_1–42. In contrast, higher levels of the cytokines IL-10, IL-13, IL-4, and IL-lα were associated with decreased tau pathology only in the absence of APOE ε4. Furthermore, higher Iba1 microglia density was associated with increased tau pathology in APOE ε4 positive participants. Compared to APOE ε4 negative participants, APOE ε4 carriers appear to adopt a potentially toxic association between inflammatory markers and Aβ_1–42…