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Characterization of Brain Lysosomal Activities in GBA-Related and Sporadic Parkinson's Disease and Dementia with Lewy Bodies.

ABSTRACT: Mutations in the GBA gene, encoding the lysosomal hydrolase glucocerebrosidase (GCase), are the most common known genetic risk factor for Parkinson's disease (PD) and dementia with Lewy bodies (DLB). The present study aims to gain more insight into changes in lysosomal activity in different brain regions of sporadic PD and DLB patients, screened for GBA variants. Enzymatic activities of GCase, ?-hexosaminidase, and cathepsin D were measured in the frontal cortex, putamen, and substantia nigra (SN) of a cohort of patients with advanced PD and DLB as well as age-matched non-demented controls (n?=?15/group) using fluorometric assays. Decreased activity of GCase (-?21%) and of cathepsin D (-?15%) was found in the SN and frontal cortex of patients with PD and DLB compared to controls, respectively. Population stratification was applied based on GBA genotype, showing substantially lower GCase activity (~?-?40%) in GBA variant carriers in all regions. GCase activity was further significantly decreased in the SN of PD and DLB patients without GBA variants in comparison to controls without GBA variants. Our results show decreased GCase activity in brains of PD and DLB patients with and without GBA variants, most pronounced in the SN. The results of our study confirm findings from previous studies, suggesting a role for GCase in GBA-associated as well as sporadic PD and DLB.

SUBMITTER: Moors TE

PROVIDER: S-EPMC6400877 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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Characterization of Brain Lysosomal Activities in GBA-Related and Sporadic Parkinson's Disease and Dementia with Lewy Bodies.

Moors Tim E TE Paciotti Silvia S Ingrassia Angela A Quadri Marialuisa M Breedveld Guido G Tasegian Anna A Chiasserini Davide D Eusebi Paolo P Duran-Pacheco Gonzalo G Kremer Thomas T Calabresi Paolo P Bonifati Vincenzo V Parnetti Lucilla L Beccari Tommaso T van de Berg Wilma D J WDJ

Molecular neurobiology 20180608 2

Mutations in the GBA gene, encoding the lysosomal hydrolase glucocerebrosidase (GCase), are the most common known genetic risk factor for Parkinson's disease (PD) and dementia with Lewy bodies (DLB). The present study aims to gain more insight into changes in lysosomal activity in different brain regions of sporadic PD and DLB patients, screened for GBA variants. Enzymatic activities of GCase, β-hexosaminidase, and cathepsin D were measured in the frontal cortex, putamen, and substantia nigra (S ...[more]

PMID: 29948939

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Dataset Information

Characterization of Brain Lysosomal Activities in GBA-Related and Sporadic Parkinson's Disease and Dementia with Lewy Bodies.

Publications

Characterization of Brain Lysosomal Activities in GBA-Related and Sporadic Parkinson's Disease and Dementia with Lewy Bodies.

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