Prospective role of PAK6 and 14-3-3γ as biomarkers for Parkinson’s disease

Abstract Parkinson’s disease (PD) is a progressive neurodegenerative disorder mainly distinguished by sporadic aetiology, although a genetic component is also well established. Variants in the LRRK2 gene are associated with both familiar and sporadic forms of the disease. We have previously shown that PAK6 and 14-3-3γ interact with and regulate the activity of LRRK2. In this study, we quantify the total amount of PAK6 and 14-3-3γ both in post-mortem tissue and in plasma samples to explore their potential as novel biomarkers for PD. The amount of PAK6 and 14-3-3γ is significantly different in PD patients compared to healthy subjects; moreover, PAK6 also varies with the presence of the G2019S mutation in the LRRK2 gene. These observations were further confirmed by generalized linear models. We suggest that changes of PAK6 and 14-3-3γ in plasma represent a shared readout for patients affected by sporadic and LRRK2-related PD and they may be added in a broader panel of biomarkers for PD.