High-fat diet generally exacerbates, but is sometimes protective against, cognitive dysfunction in female AD mice depending on genetic background.

Our results suggest that AD risk and progression depends on an interaction between sex, genetic background, and response to diet. We observed that females are more susceptible to AD- related cognitive decline and metabolic dysfunction when fed either chow or HFD, and we identified a novel genetic locus contributing to increased vulnerability to AD- and HFD-related cognitive decline in females. Future analyses aim to identify genetic and molecular targets that contribute to AD pathogenesis sensitized by sex and HFD that may be exploited to delay, prevent or treat AD.