Comparative plasma metabolomic analysis to identify biomarkers for lead-induced cognitive impairment.

Background: Lead (Pb), an environmental neurotoxicant, is known to induce cognitive impairment. Neuroinflammation and oxidative stress in the brain tissue are common pathogenetic links to Pb-induced cognitive impairment. There are no existing biomarkers to evaluate Pb-reduced cognition. Plasma metabolites are the readout of the biological functions of the host, making it a potential biomarker for assessing heavy metal-induced cognitive impairment.

Methods: The present report aims to identify the plasma metabolite changes under conditions of high plasma Pb levels and low cognition.

Results: We conducted a comparative plasma metabolomic analysis on two groups of adults those with low plasma Pb level and high cognition vs. those with high plasma Pb level and low cognition and identified 20 dysregulated metabolites. In addition, we found a significant reduction in docosahexaenoic acid, glycoursodeoxycholic acid, and arachidonic acid, and significant induction of p-cresol sulfate and phenylacetyl-l-glutamine. Gene Ontology enrichment analysis highlighted the importance of these plasma metabolites in brain functions and neurodegenerative diseases such as Parkinson's disease.

Conclusions: The findings of this report provide novel insights into the use of plasma metabolites to assess metal-induced cognitive impairment.