Increased Oxidative Stress Markers in Cerebrospinal Fluid from Healthy Subjects with Parkinson's Disease-Associated Gene Mutations

Mutations in the leucine-rich repeat kinase 2 () gene are the most frequent cause of inherited Parkinson's disease (PD). The most common PD-associated mutation, G2019S, induces increased production of reactive oxygen species . We therefore hypothesized that individuals with PD-associated mutations might have increased concentrations of oxidative stress markers and/or decreased total antioxidant capacity (TAC) in their cerebrospinal fluid (CSF). We measured two oxidative stress markers, namely 8-hydroxy-2'-deoxyguanosine (8-OHdG) and 8-isoprostane (8-ISO), and TAC in CSF from mutation-bearing PD patients ( PD = 19), sporadic PD patients (sPD = 31), and healthy control subjects with or without these mutations ( CTL = 30, CTL = 27). 8-OHdG and 8-ISO levels were increased in CTL subjects, while TAC was similar between groups. 8-ISO was negatively correlated, and TAC was positively correlated, with Montreal Cognitive Assessment scores in PD, CTL, and CTL subjects. Correlations in both groups of PD patients between the two oxidative stress markers and Unified Parkinson Disease Rating Scale Total scores were weak, while TAC was negatively correlated with these scores. These findings suggest that oxidative stress may be increased in the CNS in healthy individuals with PD-associated mutations. Further, TAC may decrease in the CNS with the progression of PD, and when cognitive impairment is present regardless of the presence or absence of PD.