This $431,750 Project Grant award from the National Institute on Aging (CFDA 93.866 - Aging Research) to Arizona State University will investigate the interaction between biological sex and APOE genotype in modulating Alzheimer's disease (AD) risk. Through this 2-year award, the researchers will use gene editing technology to introduce various APOE genotypes into isogenic human induced pluripotent stem cell (hiPSC) lines with different sex chromosome complements. These cell lines will then be used in neuronal, astrocytic, and microglia culture systems to determine how APOE and biological sex interact to influence amyloid-beta processing, tau hyperphosphorylation, and global transcriptional changes relevant to AD risk. The goal is to gain a more thorough understanding of the mechanisms by which APOE and sex modulate the likelihood of AD onset, with the potential to inform future therapeutic interventions.
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