Longitudinal Measurements of Glucocerebrosidase activity in Parkinson's patients. Issue 10 (5th September 2020)

• Record Type: Journal Article
• Authors: 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
• Other Names: Marek Kenneth investigator.; Siderowf Andrew investigator.; Seibyl John investigator.; Coffey Christopher investigator.; Tanner Caroline investigator.; Tosun‐Turgut Duygu investigator.; Shaw Leslie M investigator.; Trojanowski John Q investigator.; Singleton Andrew investigator.; Kieburtz Karl investigator.; Toga Arthur investigator.; Mollenhauer Brit investigator.; Galasko Douglas investigator.; Chahine Lana M investigator.; Poewe Werner investigator.; Poston Kathleen investigator.; Bressman Susan investigator.; Reimer Alyssa investigator.; Arnedo Vanessa investigator.; Clark Adrienne investigator.; Frasier Mark investigator.; Kopil Catherine investigator.; Chowdhury Sohini investigator.; Sherer Todd investigator.; Casaceli Cynthia investigator.; Dorsey Ray investigator.; Wilson Renee investigator.; Mahes Sugi investigator.; Salerno Christina investigator.; Crawford Karen investigator.; Casalin Paola investigator.; Malferrari Giulia investigator.; Weisz Mali Gani investigator.; Orr‐Urtreger Avi investigator.; Montine Thomas investigator.; Baglieri Chris investigator.; Christini Amanda investigator.; Russell David investigator.; Dahodwala Nabila investigator.; Giladi Nir investigator.; Factor Stewart investigator.; Hogarth Penelope investigator.; Standaert David investigator.; Hauser Robert investigator.; Jankovic Joseph investigator.; Saint‐Hilaire Marie investigator.; Richard Irene investigator.; Shprecher David investigator.; Fernandez Hubert investigator.; Brockmann Katrina investigator.; Rosenthal Liana investigator.; Barone Paolo investigator.; Espay Alberto investigator.; Rowe Dominic investigator.; Marder Karen investigator.; Santiago Anthony investigator.; Hu Shu‐Ching investigator.; Isaacson Stuart investigator.; Martinez Javiar Ruiz investigator.; Tolosa Eduardo investigator.; Tai Yen investigator.; Politis Marios investigator.; Smejdir Debra investigator.; Rees Linda investigator.; Williams Karen investigator.; Kausar Farah investigator.; Richardson Whitney investigator.; Willeke Diana investigator.; Peacock Shawnees investigator.; Sommerfeld Barbara investigator.; Freed Alison investigator.; Wakeman Katrina investigator.; Blair Courtney investigator.; Guthrie Stephanie investigator.; Harrell Leigh investigator.; Hunter Christine investigator.; Thomas Cathi‐Ann investigator.; James Raymond investigator.; Zimmerman Grace investigator.; Brown Victoria investigator.; Mule Jennifer investigator.; Hilt Ella investigator.; Ribb Kori investigator.; Ainscough Susan investigator.; Wethington Misty investigator.; Ranola Madelaine investigator.; Mejia Santana Helen investigator.; Moreno Juliana investigator.; Raymond Deborah investigator.; Speketer Krista investigator.; Carvajal Lisbeth investigator.; Carvalo Stephanie investigator.; Croitoru Ioana investigator.; Garrido Alicia investigator.; Payne Laura Marie investigator.; Viswanth Veena investigator.; Severt Lawrence investigator.; Facheris Maurizio investigator.; Soares Holly investigator.; Mintun Mark A investigator.; Cedarbaum Jesse investigator.; Taylor Peggy investigator.; Biglan Kevin investigator.; Vandenbroucke Emily investigator.; Haider Sheikh Zulfiqar investigator.; Bingol Baris investigator.; Fischer Tanya investigator.; Sardi Pablo investigator.; Forrat Remi investigator.; Reith Alastair investigator.; Egebjerg Jan investigator.; Hillert Gabrielle Ahlberg investigator.; Saba Barbara investigator.; Min Chris investigator.; Umek Robert investigator.; Mather Joe investigator.; De Santi Susan investigator.; Post Anke investigator.; Boess Frank investigator.; Taylor Kirsten investigator.; Grachev Igor investigator.; Avbersek Andreja investigator.; Muglia Pierandrea investigator.; Merchant Kaplana investigator.; Tauscher Johannes investigator.;
• Is Part Of: Annals of clinical and translational neurology. Volume 7:Issue 10(2020)
• Page Start: 1816
• Page End: 1830
• Publication Date: 2020-09-05
• Subjects: Nervous system -- Diseases -- Periodicals; Neurology -- Periodicals; 616.8005
• DOI: 10.1002/acn3.51164
• Languages: English
• ISSNs: 2328-9503

Abstract

Abstract: Objective: Reduction 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. Methods: We 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, n = 392; controls, n = 175) were fully sequenced for GBA variants by means of genome‐wide genotyping arrays, whole‐exome sequencing, whole‐genome sequencing, Sanger sequencing, and RNA‐sequencing. Results: Fifty‐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, n = 20; controls, n = 5), activity was significantly lower in PD carriers than control carriers (9.53 µ mol/L/h vs. 11.68 µ mol/L/h, P = 0.035). Glucocerebrosidase activity was moderately ( r = 0.45) 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. Interpretation: GCase 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.