Apolipoprotein E (ApoE) 4 exacerbates pattern separation deficits and amyloid pathology in a combined humanized knock‐in Apolipoprotein E, Amyloid, and Tau model of Alzheimer's Disease

These results suggest even minor changes in amyloid processing (in App^NL mice) seem to synergize with ApoE4 as a driving mechanism of pattern separation deficits, detectable as early as 6 months old. This effect seems to be independent of insoluble amyloid accumulation, which was significantly increased in the hippocampus only after 9 months. Ongoing work examines whether soluble amyloid oligomers and ApoE4's direct impact on neurogenesis contribute to the pattern separation deficits. Nonetheless, we observed a reproducible deficit in LD performance in these mice compatible with early pattern separation deficits.