Profiling the Biochemical Signature of GBA-Related Parkinson's Disease in Peripheral Blood Mononuclear Cells

Background GBA mutations are the commonest genetic risk factor for Parkinson's disease (PD) and also impact disease progression. Objective The objective of this study was to define a biochemical profile that could distinguish GBA-PD from non-mutated PD. Methods 29 GBA-PD, 37 non-mutated PD, and 40 controls were recruited; alpha-synuclein levels in plasma, exosomes, and peripheral blood mononuclear cells were analyzed, GCase and main GCase-related lysosomal proteins in peripheral blood mononuclear cells were measured. Results Assessment of plasma and exosomal alpha-synuclein levels did not allow differentiation between GBA-PD and non-mutated PD; conversely, measurements in peripheral blood mononuclear cells clearly distinguished GBA-PD from non-mutated PD, with the former group showing significantly higher alpha-synuclein levels, lower GCase activity, higher LIMP-2, and lower Saposin C levels. Conclusion We propose peripheral blood mononuclear cells as an easily accessible and manageable model to provide a distinctive biochemical profile of GBA-PD, potentially useful for patient stratification or selection in clinical trials. (c) 2021 International Parkinson and Movement Disorder Society

Automated summary

This study demonstrates that measuring biomarkers in peripheral blood mononuclear cells can clearly distinguish GBA-PD from non-mutated PD, with significant differences in alpha-synuclein levels, GCase activity, LIMP-2, and Saposin C levels between the two groups.