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 International Parkinson and Movement Disorder Society.

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

Avenali M.;Cerri S.;Tassorelli C.;Valente E. M.;Blandini F.
2021

Abstract

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 International Parkinson and Movement Disorder Society.
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11571/1421635
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