Changes of fatty acid metabolism in FA 26:0, FA 22:2 and FA 24:1 are associated with leukoaraiosis in the elderly

Abstract Background: Cerebrovascular diseases in the elderly are associated with abnormal lipids metabolism. Although cerebral small vascular disease like Leukoaraiosis (LA) is reported to be common among the elderly with occurrence and progression of neurological disease, there are no effective treatments and even biomarkers screening for LA due to the limited understanding of its biochemical processes. Here, we employ untargeted and targeted lipidomic strategies to provide insights into LA onset associated with lipid disturbance. Results: A total of 122 participants were recruited, following exclusion criteria and propensity score matching, the final cohort consisted of 16 LA patients and 18 control subjects (CK). Untargeted lipid profiling identified 50 significantly different metabolites between LA and CK groups. Pathway enrichment and structural equation modeling demonstrated that fatty acid (FA) metabolism had significant impacts on LA onset. Compared with CK group, targeted free fatty acid (FFA) profiling revealed a significant decrease of FA C22:2 as well as FA 24:1 and increase of FA 26:0 in LA group, which were proved as potential biomarkers by logistic regression and decision curve models. WGCNA coupling with correlation analysis unveiled FA 26:0 mainly came out of ceramide (18:1/26:0), and FA 24:1 was initiated from phosphatidylcholine hub-transformed by lysophosphatidic acid (20:5), and FA 22:2 was mainly generated through glycerolipid. Conclusion: Our results demonstrated potential FFA biomarkers for LA screening, and illuminated preliminary metabolism process from lipid disturbance to FFAs alternation in LA patients, implying regulation of FA 26:0, FA 22:2 and FA 24:1 constituting in-depth mechanism for further studies of LA.