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; α‐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 α‐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 α‐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.

© 2021 The Authors.

Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society