This Project Grant from the National Institute on Aging, part of the Department of Health and Human Services, provides $4,563,558 under the Aging Research program (CFDA 93.866) to the Jackson Laboratory from September 15, 2022 to August 31, 2025.
The funding supports research to model the genetic interaction between the Klotho and ApoE alleles in Alzheimer's disease. Specifically, the awardee will characterize new mouse models harboring relevant human variants in both Klotho and ApoE to determine the physiological processes altered by Klotho as a protective factor against Alzheimer's disease in ApoE4 carriers. The research aims to validate and characterize this genetic interaction observed in human studies, and identify molecular signatures shared between the mouse models and human Alzheimer's stratified by Klotho haplotype. The outcomes will provide a biological basis for Klotho's apparent protection against Alzheimer's disease in ApoE4 carriers, to guide potential genotype-targeted treatments.
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