Dr Margaret Flanagan

I am a physician–scientist and board-certified neuropathologist whose work focuses on unraveling the mechanisms that drive dementia and related neurodegenerative diseases. My research bridges diagnostic neuropathology, brain banking, and cutting-edge digital pathology. I direct a high-complexity CLIA-certified plasma and CSF biomarker laboratory, lead the Nun Study of Aging and Alzheimer’s Disease, and co-lead multiple national and international collaborations. Much of my work explores how mixed pathologies—such as TDP-43, tau, and vascular brain lesions—interact to shape clinical outcomes. To push beyond traditional histology, I leverage spatial transcriptomics to map gene expression directly onto neuropathological lesions, uncovering cell-specific vulnerabilities within their microenvironment. By integrating these high-resolution molecular datasets with deeply phenotyped longitudinal cohorts such as the Nun Study and the Honolulu-Asia Aging Study (HAAS), we can link decades of clinical, cognitive, and lifestyle data to molecular signatures in brain tissue. This unique approach enables me to investigate how genetic risk factors, vascular pathology, and protein aggregates interact across the lifespan to shape disease trajectories, with the ultimate goal of identifying novel biomarkers and therapeutic targets.