Alteration of Metabolic Profile During the Progression of Alzheimer’s Disease

Abstract Alzheimer's disease (AD) is a progressive neurodegenerative disorder that threatens the population health of older adults. However, the mechanisms of how altered metabolism involving in AD pathology are poorly understood. The aim of the study was to identify potential biomarkers of AD and discover metabolomic changes that produced during the progression of the disease. The Gas chromatography-mass spectrometry (GC-MS) was used to measure the concentrations of serum metabolites in a cohort of subjects with AD (n = 88) and cognitively normal control (CN) (n = 85). The patients were classified as very mild, mild, moderate, and severe. Serum metabolic profiles were analyzed by multivariate and univariate approaches. The least absolute shrinkage and selection operator (LASSO) logistic regression was applied to identify potential biomarkers of AD. Biofunctional enrichment analysis was performed using the Kyoto Encyclopedia of Genes and Genomes. Our results revealed considerable separation between the AD and CN. Six metabolites were identified as potential biomarkers of AD (AUC > 0.85), and the diagnostic model of three metabolites could predict the risk for AD with high accuracy (AUC = 0.984). The metabolic enrichment analysis revealed that carbohydrate metabolism deficiency and disturbance of amino acids, fatty acids, and lipids metabolism are involved in AD progression. Especially, pathway analysis highlighted that l − glutamate participated in four crucial nervous system pathways (including GABAergic synapse, glutamatergic synapse, retrograde endocannabinoid signaling and synaptic vesicle cycle). Carbohydrate metabolism deficiency, amino acids dysregulation, fatty acids and lipids metabolism disorders were pivotal events in AD progression. Our study may provide novel insights into the role of metabolic disorders in AD pathogenesis and identify new markers for AD diagnosis.