Schedule of Events | Symposia

Sketchpad Series

Relationship between Polygenetic Risk Score of BrainAge and plasma biomarkers in the A4/eLearn Study.

Poster Session D - Monday, March 31, 2025, 8:00 – 10:00 am EDT, Back Bay Ballroom/Republic Ballroom

Jorge Garcia Condado^1,2,3, Colin Birkenbihl³, Jesus M Cortes^1,4, Ibai Diez^1,4,5,6, Rachel F Buckley^3,7; ¹Computational Neuroimaging Lab, Biobizkaia Health Research Institute, ²Universidad del Pais Vasco (UPV/EHU), ³Massachusetts General Hospital, Department of Neurology, ⁴IKERBASQUE, ⁵Gordon Center for Medical Imaging, Department of Radiology, ⁶Athinoula A. Martinos Center for Biomedical Imaging, ⁷Melbourne School of Psychological Sciences, University of Melbourne

Tools such as Brain Age Gap, which measures the discrepancy between chronological and predicted brain age based on neuroimaging, and Polygenic Risk Scores (PRS), which quantify genetic predisposition to specific traits like accelerated brain aging, are proving valuable in elucidating the genetic underpinnings of neurodegeneration. In this study, we analyzed genetic information and plasma biomarkers from the A4/ELearn study on 3014 cognitively normal subjects (71.4 +- 4.6 age; 40.3% male). PRS of BrainAge models were calculated for each subject using the summary GWAS statistics of Wen et. al, Nature Communications 2024 for three types of BrainAge models: Grey Matter (GM), White Matter (WM) and Functional Connectivity (FC). We focused on 6 plasma biomarkers from the study: pTau217, FP42/FP40, plasma APOE4 prtoein levels, GFAP, Neuro Filament Light Chain and pTauC2. We used a general linear model to study the association between the biomarkers with PRS and with the interaction between age and PRS for each BrainAge model. We found that the interaction between age and GM PRS, was positively associated with pTAU217 (p-value=0.0073) and pTauC2 (p-value=0.040). The GM PRS alone was also associated with pTauC2 after adjusting for age and the interaction (p-value=0.042). Moreover, the interaction between age and WM PRS was associated positively with FP42/40 (p-value=0.020) and pTauC2 (p-value=0.043). This study highlights the significance of genetic factors contributing to accelerated brain aging and its association with neurodegenerative biomarkers. It's noteworthy that the effects of these genetic predispositions often become apparent only when combined with aging.

Topic Area: METHODS: Neuroimaging