James A. Goodman1, Peter Cheng-Te Chou1, Zhiyong Xie1, Kelly R. Bales2
1Precision Medicine, Pfizer Inc, Groton, CT, United States; 2Neuroscience Research Unit, Pfizer Inc, Cambridge, MA, United States
Then&[epsilon]4 allele of the apolipoprotein E (ApoE) gene is associated with increased risk of Alzheimers disease (AD) combined with an earlier age of disease onset. Little is known about how the &[epsilon]4 allele confers disease susceptibility, so mouse models expressing human ApoE alleles in the place of endogenous mouse ApoE protein by targeted replacement serve as ideal in vivo models to investigate how the &[epsilon]4 allele may influence normal brain function. We utilized structural, functional, and metabolic MRI techniques to characterize mice that are homozygous for human Apo&[epsilon]2, &[epsilon]3, and &[epsilon]4, at 14 and 20 months of age.