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Abstract #3603

MRI Assessment of Sex Differences in APOEε4 Knock-in in Rat Brains

Loi Vinh Do1, Aarti Mishra2,3, Adam Scott Bernstein1, Marc Lindley1, Chidi Ugonna1, Nan-kuei Chen1, Roberta Brinton3,4, and Theodore Trouard1

1Biomedical Engineering, University of Arizona, Tucson, AZ, United States, 2Department of Clinical Therapeutics, USC School of Pharmacy, University of Southern California, Los Angeles, CA, United States, 3Center for Innovation in Brain Science, University of Arizona, Tucson, AZ, United States, 4Department of Pharmacology, University of Arizona, Tucson, AZ, United States

Using a humanized APOEε4 gene knock-in ex-vivo rat brain model, the individual and combined impact of sex and APOEε4 genotype on white matter microstructure was measured using high T2-weighted and diffusion weighted MRI. Total brain volumes showed a significant sexual dimorphism in WT as well as APOEε4 animals, with the females having significantly lower volumes. Both volumetric and diffusion MRI measures were able to show trends of sexual dimorphism as well as genotype effect. These findings were supported with metabolomic data suggesting reduction in glucose utilization and possible shift to fatty acids derived from white matter catabolism as a fuel source.

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