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Brain microglial activation increased in glucocerebrosidase (GBA1) mutation carriers

Lookup NU author(s): Professor Nicola PaveseORCiD, Professor David BrooksORCiD



This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Background: GBA1 is a common genetic risk factor for Parkinson disease which exhibits incomplete penetrance. Objective: To measure microglial activation and dopamine integrity in GBA1 mutation carriers without Parkinson disease, compared to controls. Methods: We performed PET scans on nine GBA1 mutation carriers without Parkinson disease and 29 age matched controls. We measured microglial activation as 11C-(R)-PK11195 binding potentials, and dopamine terminal integrity with 18F-DOPA influx constants.. Results: 11C-(R)-PK11195 binding potentials were increased in the substantia nigra of GBA1 carriers compared to controls (Student’s t test, right t=-3.4 p=0.0022, left t=-4.5, p=0.0001). Statistical Parametric Mapping also localised significantly increased 11C-(R)-PK11195 binding potential in the occipital and temporal lobes, cerebellum, hippocampus, and mesencephalon. Degree of hyposmia correlated with nigral 11C-(R)-PK11195 BPND (Spearman’s rank, right; p=0.031, left; p=0.006). Mean striatal 18F-DOPA uptake was similar to healthy controls. Conclusions: In vivo 11C-(R)-PK11195 PET imaging detects neuroinflammation in brain regions susceptible to Lewy pathology in GBA1 mutation carriers.

Publication metadata

Author(s): Mullin S, Stokholm MG, Hughes D, Mehta A, Parbo P, Hinz R, Pavese N, Brooks DJ, Schapira AHV

Publication type: Article

Publication status: Published

Journal: Movement Disorders

Year: 2021

Volume: 36

Issue: 3

Pages: 774-779

Print publication date: 01/03/2021

Online publication date: 05/12/2020

Acceptance date: 19/10/2020

Date deposited: 26/10/2020

ISSN (print): 0885-3185

ISSN (electronic): 1531-8257

Publisher: John Wiley & Sons, Inc.


DOI: 10.1002/mds.28375


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Funder referenceFunder name
National Institute for Health Research