Targeted Metabolomic Analysis in Alzheimer’s Disease Plasma and Brain Tissue in Non-Hispanic Whites
Abstract
BACKGROUND: Metabolites are biological compounds reflecting the functional activity of organs and tissues. Understanding metabolic changes in Alzheimer's disease (AD) can provide insight into potential risk factors in this multifactorial disease and suggest new intervention strategies or improve non-invasive diagnosis. OBJECTIVE: In this study, we searched for changes in AD metabolism in plasma and frontal brain cortex tissue samples and evaluated the performance of plasma measurements as biomarkers. METHODS: This is a case-control study with two tissue cohorts: 158 plasma samples (94 AD, 64 controls; Texas Alzheimer's Research and Care Consortium - TARCC) and 71 postmortem cortex samples (35 AD, 36 controls; Banner Sun Health Research Institute brain bank). We performed targeted mass spectrometry analysis of 630 compounds (106 small molecules: UHPLC-MS/MS, 524 lipids: FIA-MS/MS) and 232 calculated metabolic indicators with a metabolomic kit (Biocrates MxP® Quant 500). RESULTS: We discovered disturbances (FDR≤0.05) in multiple metabolic pathways in AD in both cohorts including microbiome-related metabolites with pro-toxic changes, methylhistidine metabolism, polyamines, corticosteroids, omega-3 fatty acids, acylcarnitines, ceramides, and diglycerides. In AD, plasma reveals elevated triglycerides, and cortex shows altered amino acid metabolism. A cross-validated diagnostic prediction model from plasma achieves AUC = 82% (CI95 = 75-88%); for females specifically, AUC = 88%…
How strong is the evidence?
Evidence Hub reads this as a case-control. Its evidence level is 4 of 5 (Low · observational). Observational designs can show an association but not prove cause.
Read the paper
Related studies
- Metabolic Syndrome: Updates on Pathophysiology and Management in 2021
- Environmental pollutants as risk factors for neurodegenerative disorders: Alzheimer and Parkinson diseases
- Antioxidants, inflammation and cardiovascular disease
- Application of Metabolomics in Alzheimer’s Disease
- Nutritional Importance of Carotenoids and Their Effect on Liver Health: A Review
- Nutritional essentiality of sulfur in health and disease
Go deeper in Evidence Hub
Evidence Hub adds a study data sheet (design, sample size, evidence level, key numbers), an AI summary and a chat grounded in the paper's text.