Abstract #3603

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

Loi Vinh Do¹, Aarti Mishra^2,3, Adam Scott Bernstein¹, Marc Lindley¹, Chidi Ugonna¹, Nan-kuei Chen¹, Roberta Brinton^3,4, 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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