Reduced glucocerebrosidase activity in monocytes from patients with Parkinson’s disease

Farzaneh Atashrazm, Deborah Hammond, Gayathri Perera, Carol Dobson-Stone, Nicole Mueller, Russell Pickford, Woojin Scott Kim, John B. Kwok, Simon J. G. Lewis, Glenda M. Halliday*, Nicolas Dzamko

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

81 Citations (Scopus)
22 Downloads (Pure)

Abstract

Missense mutations in glucocerebrosidase (GBA1) that impair the activity of the encoded lysosomal lipid metabolism enzyme (GCase) are linked to an increased risk of Parkinson’s disease. However, reduced GCase activity is also found in brain tissue from Parkinson’s disease patients without GBA1 mutations, implicating GCase dysfunction in the more common idiopathic form of Parkinson’s disease. GCase is very highly expressed in monocytes, and thus we measured GCase activity in blood samples from recently diagnosed Parkinson’s disease patients. Flow cytometry and immunoblotting assays were used to measure levels of GCase activity and protein in monocytes and lymphocytes from patients with Parkinson’s disease (n = 48) and matched controls (n = 44). Gene sequencing was performed to screen participants for GBA1 missense mutations. In the Parkinson’s disease patients, GCase activity was significantly reduced in monocytes, but not lymphocytes, compared to controls, even when GBA1 mutation carriers were excluded. Monocyte GCase activity correlated with plasma ceramide levels in the Parkinson’s disease patients. Our results add to evidence for GCase dysfunction in idiopathic Parkinson’s disease and warrant further work to determine if monocyte GCase activity associates with Parkinson’s disease progression.

Original languageEnglish
Article number15446
Pages (from-to)1-12
Number of pages12
JournalScientific Reports
Volume8
Issue number1
DOIs
Publication statusPublished - 1 Dec 2018
Externally publishedYes

Bibliographical note

Copyright the Author(s) 2018. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.

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