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Abstract #3652

Rapamycin treatment increases cerebral blood flow and attenuates anxiety in pre-symptomatic APOE4 mice: effects of sex and APP transgene

Ishita Parikh1, David Ma1, Jared D. Hoffman1,2, Amy Wang3, and Ai-Ling Lin1,2,4

1Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY, United States, 2Pharmacology and Nutritional Sciences, University of Kentucky, Lexington, KY, United States, 3Harvard University, Cambridge, MA, United States, 4Biomedical Engineering, University of Kentucky, Lexington, KY, United States

APOE4 is the strongest genetic risk factor for Alzheimer’s disease (AD). Pre-symptomatic APOE4 carriers have developed neurovascular deficits decades before amyloid beta (Aβ) aggregation. Here we show that with Rapamycin treatment for 16 weeks, pre-symptomatic APOE4 mice had restored cerebral blood flow (CBF) and attenuated anxiety, compared to those of APOE3 mice. The CBF restorations were particularly significant in female mice or those with APP transgene. As Rapamycin and MRI and are readily to be used in humans, the findings may provide valuable information for future clinical trials to prevent AD for APOE4 carriers.

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