Learn Mem 2020 Sep; 27(9):355-371
Individual differences in cognitive decline during normal aging and Alzheimer's disease (AD) are common, but the molecular mechanisms underlying these distinct outcomes are not fully understood. We utilized a combination of genetic, molecular, and behavioral data from a mouse population designed to model human variation in cognitive outcomes to search for the molecular mechanisms behind this population-wide variation. Specifically, we used a systems genetics approach to relate gene expression to cognitive outcomes during AD and normal aging. Statistical causal-inference Bayesian modeling was used to model systematic genetic perturbations matched with cognitive data that identified astrocyte and microglia molecular networks as drivers of cognitive resilience to AD. Using genetic mapping, we identified
Heuer, Sarah E; Neuner, Sarah M; Hadad, Niran; O'Connell, Kristen M S; Williams, Robert W; Philip, Vivek M.; Gaiteri, Chris; and Kaczorowski, Catherine, "Identifying the molecular systems that influence cognitive resilience to Alzheimer's disease in genetically diverse mice." (2020). Faculty Research 2020. 162.