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.