SWATH Mass Spectrometry-Based CSF Proteome Profile of -Linked Parkinson's Disease Patients.

β-glucocerebrosidase ()-associated mutations are a significant risk factor for Parkinson's disease (PD) that aggravate the disease pathology by upregulating the deposition of α-Synuclein (α-Syn). The resultant clinical profile varies for PD patients without mutations. The current study aimed to identify the proteomic targets involved in the pathogenic pathways leading to the differential clinical presentation of -associated PD. CSF samples ( = 32) were obtained from PD patients with mutations ( = 22), PD patients without mutations ( = 7), and healthy controls that were carriers of mutations ( = 3). All samples were subjected to in-gel tryptic digestion followed by the construction of the spectral library and quantitative SWATH-based analysis. CSF α-Syn levels were reduced in both PD and PD cases. Our SWATH-based mass spectrometric analysis detected 363 proteins involved in immune response, stress response, and cell signaling in various groups. Intergroup analysis showed that 52 proteins were significantly up- or downregulated in various groups. Of these 52 targets, 20 proteins were significantly altered in PD cases only while 2 showed different levels in PD patients. Our results show that the levels of several pathologically relevant proteins, including Contactin-1, Selenium-binding protein 1, Adhesion G Protein-Coupled Receptor, and Apolipoprotein E are significantly different among the sporadic and genetic variants of PD and hint at aggravated synaptic damage, oxidative stress, neuronal loss, and aggregation of α-Syn in PD cases.