Abstract
Parkinson's disease (PD) is the second most common neurodegenerative disorder following Alzheimer's disease, with a 1.5 times higher prevalence in males. Several lipid-related genetic risk factors for PD have been identified, and the brain lipid signature of PD patients is distinguishable from controls. To elucidate the molecular mechanisms underlying PD and its sex differences, we conducted a lipidomic analysis of postmortem brain samples from the primary motor cortex (Brodmann area 4) of 40 PD patients and 43 age- and sex-matched matched controls. Mass spectrometry based lipidomics analysis revealed notable differences in 95 lipid species, especially Triacylglycerols and Lysophosphatidylcholines. Notably, sex-stratified analysis suggested that mitochondrial dysfunction may explain the higher prevalence of PD in males. These findings highlight lipid dysregulation in PD and point to potential biomarkers for diagnosis, warranting further validation.