Plasma Proteome Signatures as Transdiagnostic Markers of Clinical Severity in Neurodegenerative Diseases​

Poster Session E - Monday, March 9, 2026, 2:30 – 4:30 pm PDT, Fairview/Kitsilano Ballrooms

Ethan Terman¹, Lior Sanilevich¹; ¹New York University

Neurodegenerative disorders such as Alzheimer's disease (AD), Parkinson's disease (PD), and frontotemporal dementia (FTD) share molecular pathologies including synaptic dysfunction and immune dysregulation, yet clinical severity varies widely and is inadequately captured by diagnostic categories alone. Plasma proteomics offers a scalable, minimally invasive approach for biomarker discovery, potentially identifying transdiagnostic markers that better index disease burden and functional decline. This literature synthesis reviewed studies from PubMed, medRxiv, and Nature Portfolio published between December 2025 and January 2026, focusing on plasma proteomics in AD, PD, and FTD cohorts (n > 500 preferred), with outcomes tied to clinical severity scales like CDR and UPDRS. Extracted analyses included differential protein abundance, multivariate prediction models, and pathway enrichment; no primary data analysis was conducted. Findings reveal shared transdiagnostic markers, such as immune, synaptic, and axonal proteins, associated with severity across disorders, suggesting convergent mechanisms of functional decline. Disease-specific profiles include tau-associated and apoptotic pathways in AD, extracellular matrix and ER stress in PD, and cytoskeletal proteins in FTD. Plasma proteins correlate more consistently with severity than diagnostic distinctions, and multivariate models outperform single biomarkers in predicting impairment. In conclusion, plasma proteomics identifies transdiagnostic markers of clinical severity, with shared immune and synaptic pathways underlying impairment; disease-specific signatures enhance diagnostic resolution, and severity-based models surpass categorical diagnoses. Integrating these biomarkers with cognitive measures could improve disease modeling and support transdiagnostic approaches to cognitive decline.

Topic Area: NEUROANATOMY