Alzheimer’s disease (AD), the leading cause of dementia in the elderly, is a progressive and fatal neurodegenerative disorder that affects 40–50 million people worldwide. AD is characterized by a continuous decline in memory, language, and cognitive functions, driven by widespread neuronal dysfunction, cortical and hippocampal atrophy, and a significant reduction in neuronal connectivity. Genome-wide association studies (GWAS) have identified over 30 genetic risk loci for AD, many of which are linked to innate immunity and microglial function. Notably, APOE and TREM2 variants are associated with high genetic risk for sporadic AD. Additionally, numerous studies have demonstrated that AD pathology spreads progressively from the medial temporal lobe to the cortex. However, the molecular mechanisms underlying the cell- and region-specific distribution of AD pathology during disease progression remain elusive.

A key focus of my lab is to apply newly developed computational methods to analyze AD-related data. Our research aims to uncover the spatial distribution of immune and glial cells in AD brains and their interactions with neurons throughout disease progression. Understanding these cellular dynamics is essential for elucidating AD pathogenesis and advancing precision medicine strategies. These insights will be critical for the development of targeted therapeutics, including small molecules designed for delivery to specific brain domains.

Related publications: mcDETECT.

In collaboration with: Bing Yao