Micol Avenali1,2, Silvia Cerri3, Gerardo Ongari3,4, Cristina Ghezzi3, Claudio Pacchetti5, Cristina Tassorelli1,2, Enza Maria Valente6,7, Fabio Blandini2,3. 1. Neurorehabilitation Unit, IRCCS Mondino Foundation, Pavia, Italy. 2. Department of Brain and Behavioural Sciences, University of Pavia, Pavia, Italy. 3. Cellular and Molecular Neurobiology Unit, IRCCS Mondino Foundation, Pavia, Italy. 4. Department of Medicine and Surgery, University of Insubria, Varese, Italy. 5. Parkinson's Disease and Movement Disorders Unit, IRCCS Mondino Foundation, Pavia, Italy. 6. Neurogenetics Research Centre, IRCCS Mondino Foundation, Pavia, Italy. 7. Department of Molecular Medicine, University of Pavia, Pavia, Italy.
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.
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.
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