BIOLOGICAL MECHANISMS ASSOCIATED WITH THE AGING BRAIN: AN INTEGRATION OF MULTIMODAL IMAGING AND GENETICS

Abstract

This thesis focuses on uncovering genes and genetic pathways subserving age-related brain alterations through an unique integration of multi-modal imaging, genotypes, and gene transcriptome profiles of aging adults. We first highlighted the potential of genetic factors in moderating differential sensitivity to brain aging through a classic genotype-brain association approach. Subsequently, we built on the classic genotype-brain association approach using polygenic variation concept, and provided a framework of analysis that was useful in identifying age-related brain regions with genetic liabilities. We also extended current work by focusing on genes which showed reversal expression in pursuit of finding whether blueprints of aging could be elucidated by scrutinizing the healthy brains across lifespan. Overall, by leveraging current state-of-the-art genetic imaging, we established and delineated the roles of genes in aging brain. Such results offered us a better understanding of the molecular mechanisms manifesting dysfunction or successful brain aging.