Longitudinal Measurements of Glucocerebrosidase activity in Parkinson's patients.
Journal
Annals of clinical and translational neurology
ISSN: 2328-9503
Titre abrégé: Ann Clin Transl Neurol
Pays: United States
ID NLM: 101623278
Informations de publication
Date de publication:
10 2020
10 2020
Historique:
received:
01
07
2020
accepted:
30
07
2020
pubmed:
6
9
2020
medline:
18
8
2021
entrez:
5
9
2020
Statut:
ppublish
Résumé
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. 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. 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 µmol/L/h vs. 11.68 µmol/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. 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.
Identifiants
pubmed: 32888397
doi: 10.1002/acn3.51164
pmc: PMC7545591
doi:
Substances chimiques
Glucosylceramidase
EC 3.2.1.45
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1816-1830Subventions
Organisme : NINDS NIH HHS
ID : U01 NS100603
Pays : United States
Investigateurs
Kenneth Marek
(K)
Andrew Siderowf
(A)
John Seibyl
(J)
Christopher Coffey
(C)
Caroline Tanner
(C)
Duygu Tosun-Turgut
(D)
Leslie M Shaw
(LM)
John Q Trojanowski
(JQ)
Andrew Singleton
(A)
Karl Kieburtz
(K)
Arthur Toga
(A)
Brit Mollenhauer
(B)
Douglas Galasko
(D)
Lana M Chahine
(LM)
Werner Poewe
(W)
Kathleen Poston
(K)
Susan Bressman
(S)
Alyssa Reimer
(A)
Vanessa Arnedo
(V)
Adrienne Clark
(A)
Mark Frasier
(M)
Catherine Kopil
(C)
Sohini Chowdhury
(S)
Todd Sherer
(T)
Cynthia Casaceli
(C)
Ray Dorsey
(R)
Renee Wilson
(R)
Sugi Mahes
(S)
Christina Salerno
(C)
Karen Crawford
(K)
Paola Casalin
(P)
Giulia Malferrari
(G)
Mali Gani Weisz
(MG)
Avi Orr-Urtreger
(A)
Thomas Montine
(T)
Chris Baglieri
(C)
Amanda Christini
(A)
David Russell
(D)
Nabila Dahodwala
(N)
Nir Giladi
(N)
Stewart Factor
(S)
Penelope Hogarth
(P)
David Standaert
(D)
Robert Hauser
(R)
Joseph Jankovic
(J)
Marie Saint-Hilaire
(M)
Irene Richard
(I)
David Shprecher
(D)
Hubert Fernandez
(H)
Katrina Brockmann
(K)
Liana Rosenthal
(L)
Paolo Barone
(P)
Alberto Espay
(A)
Dominic Rowe
(D)
Karen Marder
(K)
Anthony Santiago
(A)
Shu-Ching Hu
(SC)
Stuart Isaacson
(S)
Javiar Ruiz Martinez
(JR)
Eduardo Tolosa
(E)
Yen Tai
(Y)
Marios Politis
(M)
Debra Smejdir
(D)
Linda Rees
(L)
Karen Williams
(K)
Farah Kausar
(F)
Whitney Richardson
(W)
Diana Willeke
(D)
Shawnees Peacock
(S)
Barbara Sommerfeld
(B)
Alison Freed
(A)
Katrina Wakeman
(K)
Courtney Blair
(C)
Stephanie Guthrie
(S)
Leigh Harrell
(L)
Christine Hunter
(C)
Cathi-Ann Thomas
(CA)
Raymond James
(R)
Grace Zimmerman
(G)
Victoria Brown
(V)
Jennifer Mule
(J)
Ella Hilt
(E)
Kori Ribb
(K)
Susan Ainscough
(S)
Misty Wethington
(M)
Madelaine Ranola
(M)
Helen Mejia Santana
(H)
Juliana Moreno
(J)
Deborah Raymond
(D)
Krista Speketer
(K)
Lisbeth Carvajal
(L)
Stephanie Carvalo
(S)
Ioana Croitoru
(I)
Alicia Garrido
(A)
Laura Marie Payne
(LM)
Veena Viswanth
(V)
Lawrence Severt
(L)
Maurizio Facheris
(M)
Holly Soares
(H)
Mark A Mintun
(MA)
Jesse Cedarbaum
(J)
Peggy Taylor
(P)
Kevin Biglan
(K)
Emily Vandenbroucke
(E)
Zulfiqar Haider Sheikh
(Z)
Baris Bingol
(B)
Tanya Fischer
(T)
Pablo Sardi
(P)
Remi Forrat
(R)
Alastair Reith
(A)
Jan Egebjerg
(J)
Gabrielle Ahlberg Hillert
(GA)
Barbara Saba
(B)
Chris Min
(C)
Robert Umek
(R)
Joe Mather
(J)
Susan De Santi
(S)
Anke Post
(A)
Frank Boess
(F)
Kirsten Taylor
(K)
Igor Grachev
(I)
Andreja Avbersek
(A)
Pierandrea Muglia
(P)
Kaplana Merchant
(K)
Johannes Tauscher
(J)
Informations de copyright
© 2020 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.
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