Targeted metabolomic analysis in Parkinson's disease brain frontal cortex and putamen with relation to cognitive impairment

We performed liquid chromatography tandem mass spectrometry analysis with the targeted metabolomic kit Biocrates MxP Quant 500, in human brain cortex (Brodmann area 9) and putamen, to reveal metabolic changes characteristic of Parkinson's disease (PD) and PD-related cognitive decline. This case-control study involved 101 subjects (33 PD without dementia, 32 PD with dementia (cortex only), 36 controls). We found changes associated with PD, cognitive status, levodopa levels, and disease progression. The affected pathways include neurotransmitters, bile acids, homocysteine metabolism, amino acids, TCA cycle, polyamines, beta-alanine metabolism, fatty acids, acylcarnitines, ceramides, phosphatidylcholines, and several microbiome-derived metabolites. Previously reported levodopa-related homocysteine accumulation in cortex still best explains the dementia status in PD, which can be modified by dietary supplementation. Further investigation is needed to reveal the exact mechanisms behind this pathological change.

Automated summary

We conducted metabolomic analysis in human brain cortex and putamen to identify metabolic changes associated with Parkinson's disease and PD-related cognitive decline. The study included 101 subjects and revealed changes in neurotransmitters, bile acids, homocysteine metabolism, and other pathways. Levodopa-related homocysteine accumulation in the cortex appears to be the main factor contributing to dementia in PD, which can potentially be improved through dietary supplementation. Further investigation is needed to understand the underlying mechanisms.