Prospective role of PAK6 and 14-3-3 gamma as biomarkers for Parkinson's disease

Abstract

2.BackgroundParkinsons disease 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 disease. We have previously shown that PAK6 and 14-3-3{gamma} protein interact with and regulate the activity of LRRK2. ObjectivesThe aim of this study is to quantify PAK6 and 14-3-3{gamma} in plasma as a reliable biomarker strategy for the diagnosis of both sporadic and LRRK2-linked Parkinsons disease. MethodsAfter an initial quantification of PAK6 and 14-3-3{gamma} expression by means of Western blot in post-mortem human brains, we verified the presence of the two proteins in plasma by using quantitative ELISA tests. We analysed samples obtained from 39 healthy subjects, 40 patients with sporadic Parkinsons disease, 50 LRRK2-G2019S non-manifesting carriers and 31 patients with LRRK2-G2019S Parkinsons disease. ResultsThe amount of PAK6 and 14-3-3{gamma} is significantly different in patients with Parkinsons disease compared to healthy subjects. Moreover, the amount of PAK6 also varies with the presence of the G2019S mutation in the LRRK2 gene. Although the generalized linear models show a low association between the presence of PD and PAK6, the kinase can be added in a broader panel of biomarkers for the diagnosis of Parkinsons disease. ConclusionsChanges of PAK6 and 14-3-3{gamma} amount in plasma represent a shared readout for patients affected by sporadic and LRRK2-linked Parkinsons disease. Overall, they can contribute to the establishment of an extended panel of biomarkers for the diagnosis of Parkinsons disease.