Back to Search
Start Over
Longitudinal Measurements of Glucocerebrosidase activity in Parkinson’s patients
- Source :
- Annals of Clinical and Translational Neurology, Annals of Clinical and Translational Neurology, Vol 7, Iss 10, Pp 1816-1830 (2020)
- Publication Year :
- 2020
- Publisher :
- John Wiley and Sons Inc., 2020.
-
Abstract
- Author(s): Alcalay, Roy N; Wolf, Pavlina; Chiang, Ming Sum Ruby; Helesicova, Karolina; Zhang, Xiaokui Kate; Merchant, Kalpana; Hutten, Samantha J; Scherzer, Clemens; Caspell-Garcia, Chelsea; Blauwendraat, Cornelis; Foroud, Tatiana; Nudelman, Kelly; Gan-Or, Ziv; Simuni, Tanya; Chahine, Lana M; Levy, Oren; Zheng, Dandi; Li, Gen; Sardi, Sergio Pablo; Parkinson’s Progression Markers Initiative | Abstract: ObjectiveReduction in glucocerebrosidase (GCase; encoded by GBA) enzymatic activity has been linked to Parkinson's disease (PD). Here, we correlated GCase activity and PD phenotype in the Parkinson's Progression Markers Initiative (PPMI) cohort.MethodsWe measured GCase activity in dried blood spots from 1559 samples of participants in the inception PPMI cohort, collected in four annual visits (from baseline visit to Year-3). Participants (PD, nn=n392; controls, nn=n175) were fully sequenced for GBA variants by means of genome-wide genotyping arrays, whole-exome sequencing, whole-genome sequencing, Sanger sequencing, and RNA-sequencing.ResultsFifty-two PD participants (13.4%) and 13 (7.4%) controls carried a GBA variant. GBA status was strongly associated with GCase activity. Among noncarriers, GCase activity was similar between PD and controls. Among GBA p.E326K carriers (PD, nn=n20; controls, nn=n5), activity was significantly lower in PD carriers than control carriers (9.53nµmol/L/h vs. 11.68nµmol/L/h, Pn=n0.035). Glucocerebrosidase activity was moderately (rn=n0.45) associated with white blood cell (WBC) count. Next, we divided the noncarriers with PD to tertiles based on WBC count-corrected enzymatic activity. Members of the lower tertile had higher MDS-Unified Parkinson's Disease Rating Scale motor score in the "off" medication examination at year-III exam. Longitudinal analyses demonstrated slight reduction of activity in samples collected earlier on in the study, likely because of longer storage time.InterpretationGCase activity is associated with GBA genotype, WBC count, and among p.E326K variant carriers, with PD status. Reduced activity may also be associated with worse phenotype but longer follow up is required to confirm this observation.
- Subjects :
- Male
Gastroenterology
DISEASE
Glucocerebrosidase activity
Genotype
Dried blood
Research Articles
Sanger sequencing
General Neuroscience
Parkinson Disease
Middle Aged
Mental Status and Dementia Tests
medicine.anatomical_structure
Phenotype
Cohort
LYSOSOMAL STORAGE DISORDERS
symbols
Disease Progression
Glucosylceramidase
Female
Life Sciences & Biomedicine
RC321-571
Research Article
Adult
medicine.medical_specialty
Heterozygote
Clinical Neurology
Neurosciences. Biological psychiatry. Neuropsychiatry
symbols.namesake
Internal medicine
White blood cell
medicine
Humans
Parkinson’s Progression Markers Initiative
RC346-429
Science & Technology
business.industry
MUTATIONS
Neurosciences
1103 Clinical Sciences
Wbc count
PERFORMANCE
Mutation
Dementia
Neurology (clinical)
Neurology. Diseases of the nervous system
Neurosciences & Neurology
business
1109 Neurosciences
Glucocerebrosidase
Subjects
Details
- Language :
- English
- ISSN :
- 23289503
- Volume :
- 7
- Issue :
- 10
- Database :
- OpenAIRE
- Journal :
- Annals of Clinical and Translational Neurology
- Accession number :
- edsair.doi.dedup.....9b971a0f83da7fe3e33b13cb0976b7b4