HAI Book 2025 - Flipbook - Page 130
Duggan, Michael
14
Proteomic analyses of A-T-N reveal plasma mediators of
neurodegeneration and dementia risk
Michael Duggan1, Murat Bilgel1, Jingsha Chen2, Abhay Moghekar3, Christos Davatzikos4, Josef
Coresh5,6, Susan Resnick1, Keenan Walker1
1
Laboratory of Behavioral Neuroscience, National Institute on Aging, National Institutes of Health, Baltimore, MD, US
Department of Epidemiology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, US
3
Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, US
4
Artificial Intelligence in Biomedical Imaging Laboratory, Perelman School of Medicine, University of Pennsylvania,
Philadelphia, PA, US
5
Department of Medicine, NYU Grossman School of Medicine, New York, NY, US
6
Department of Population Health, NYU Grossman School of Medicine, New York, NY, US
2
Identifying the molecular conduits that link amyloid (A), tau (T), and neurodegeneration (N) with distinct biological
processes and downstream outcomes may illuminate important drivers of AD, while also unlocking cost-effective
biomarkers to detect vulnerable populations, estimate disease risk, or track treatment response. Using 7,268
plasma proteins measured in the Baltimore Longitudinal Study of Aging (BLSA; Figure 1; n=681) along with an A, T,
and N classification scheme that accurately predicted cognitive decline (Figure 2A), we found 1309, 592, and 254
proteins uniquely associated with A+, T+, and N+, respectively (p
