Application of Plasma Metabolomic Biomarker Panels in Early Diagnosis and Disease Staging of Alzheimer's Disease.

Background: Previous metabolomics studies on Alzheimer's disease (AD) have predominantly focused on Western populations, leaving Chinese cohorts and disease stage-specific data largely unexplored. Objectives: To characterize metabolic alterations across different clinical stages of AD in a Chinese population and identify early diagnostic biomarkers. Methods: We enrolled 172 participants, including patients with AD, mild cognitive impairment (MCI), subjective cognitive decline (SCD), vascular cognitive impairment (VCI), and healthy controls (HC). Untargeted metabolomics (LC-MS and GC-MS) was performed on plasma samples, integrated with Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) assessments. Data were analyzed using multivariate statistics, pathway enrichment, and ROC modeling. Results: Distinct metabolic profiles emerged across disease stages, with phospholipids, ceramides, and glucose metabolites prominently enriched in glycerophospholipid, sphingolipid, and glucose pathways. A 16-metabolite panel achieved robust discrimination between AD+MCI and HC+VCI+SCD (AUC = 0.804). Specific metabolites, including ceramides, dihydroceramides, phosphatidylinositol, phosphatidylcholine, and glycodeoxycholic acid, correlated significantly with cognitive function and disease progression. Conclusions: This study reveals stage-specific metabolic dysregulation in Chinese AD patients and identifies potential plasma biomarkers for early detection, offering insights into AD pathogenesis. Trial registration number ChiCTR2400092653.