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Mutations in the leucine-rich repeat kinase 2 ( LRRK2 ) gene are the most frequent cause of inherited Parkinson’s disease (PD). The most common PD-associated  LRRK2  mutation, G2019S, induces increased production of reactive oxygen species  in vitro . We therefore hypothesized that individuals with PD-associated  LRRK2  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  LRRK2  mutation-bearing PD patients ( LRRK2  PD = 19), sporadic PD patients (sPD = 31), and healthy control subjects with or without these mutations ( LRRK2  CTL = 30, CTL = 27). 8-OHdG and 8-ISO levels were increased in  LRRK2  CTL subjects, while TAC was similar between groups. 8-ISO was negatively correlated, and TAC was positively correlated, with Montreal Cognitive Assessment scores in  LRRK2  PD,  LRRK2  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  LRRK2  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.

Increased Oxidative Stress Markers in Cerebrospinal Fluid from Healthy Subjects with Parkinson’s Disease-Associated LRRK2 Gene Mutations