帕金森病脑额叶皮质和壳核中与认知障碍相关的靶向代谢组学分析

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

作者信息

Kalecký Karel, Bottiglieri Teodoro

机构信息

Institute of Biomedical Studies, Baylor University, Waco, TX, 76712, USA.

Center of Metabolomics, Institute of Metabolic Disease, Baylor Scott & White Research Institute, Dallas, TX, 75204, USA.

出版信息

NPJ Parkinsons Dis. 2023 Jun 3;9(1):84. doi: 10.1038/s41531-023-00531-y.

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, β-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.

我们使用靶向代谢组学试剂盒Biocrates MxP Quant 500，对人脑皮质（布罗德曼9区）和壳核进行液相色谱串联质谱分析，以揭示帕金森病（PD）及与PD相关的认知衰退的代谢变化特征。这项病例对照研究纳入了101名受试者（33名无痴呆的PD患者、32名有痴呆的PD患者（仅皮质受累）、36名对照）。我们发现了与PD、认知状态、左旋多巴水平及疾病进展相关的变化。受影响的代谢途径包括神经递质、胆汁酸、同型半胱氨酸代谢、氨基酸、三羧酸循环、多胺、β-丙氨酸代谢、脂肪酸、酰基肉碱、神经酰胺、磷脂酰胆碱以及几种微生物群衍生的代谢物。先前报道的皮质中左旋多巴相关的同型半胱氨酸积累，仍然是PD痴呆状态的最佳解释，这可通过膳食补充剂进行改善。需要进一步研究以揭示这种病理变化背后的确切机制。