Comprehensive serum metabolic and proteomic characterization on cognitive dysfunction in Parkinson’s disease

Abstract

Given the increased incidence of Parkinson's disease (PD) and the lack of accurate early diagnosis of PD with cognitive impairment (PD-CI), we compared the serum metabolomes and proteomes of 26 patients with PD without cognitive impairment (PD-N) and 31 patients with PD-CI by combining grade-dependent proteomics and metabolomics analyses. Logistic and linear regression analyses were performed for differential metabolic indicators, cognition, and clinical diagnosis. Ingenuity pathway analysis (IPA) was used to identify metabolites linked to different pathways. Bioinformatics revealed 16 differentially expressed proteins and 32 metabolites. The positive metabolic indicators related to the differential proteins were one sphingolipid, five phosphatidylcholines, and five long-chain fatty acids. The obtained metabolic and proteomics IPA network highlighted the central term of this network was inflammation and abnormal lipid metabolism which are prominent in PD-CI. There was a strong negative correlation between the Mini-Mental State Examination (MMSE)score and LPC (18:1). The receiver operating characteristic (ROC) of LPC (18:1) for PD-N and PD-CI showed that the area under the curve (AUC) value was 0.660 (P=0.039). In conclusion, serum LPC (18:1) is inversely linked to cognition in PD and presented its potential clinical value in distinguishing the presence or absence of cognitive impairment in PD. The deeper implication of our discovery indicates abnormal lipid metabolism is associated with changes of cognitive status and suggests the potential for possibility of immune system- inflammatory involvement.