Protein-based Diagnosis and Analysis of Co-pathologies Across Neurodegenerative Diseases: Large-Scale AI-Boosted CSF and Plasma Classification.

ABSTRACT: Neurodegenerative diseases (including Alzheimer's disease, Parkinson's disease, Frontotemporal dementia, and Dementia with Lewy bodies) pose diagnostic challenges due to overlapping pathology and clinical heterogeneity. We leveraged proteomic data from more than 21,000 cerebrospinal fluid and plasma samples to develop and validate explainable, boosting-based multi-disease AI classifiers. The models achieved weighted AUCs in the testing datasets of 0.97 for CSF and 0.88 for plasma, equivalent to traditional biomarkers. The model was validated with neuropathological and clinical data, confirming robust generalizability without any retraining. Using zero-shot learning, we classified disease subtypes including autosomal dominant AD and prodromal PD and clarified disease states for those with c

SUBMITTER: Xu Y 

PROVIDER: S-EPMC12265756 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature