Brain Microglial Activation Increased in Glucocerebrosidase (GBA) Mutation Carriers without Parkinson's disease

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

DOI

  • Stephen Mullin, Univ Plymouth, University of Plymouth, Peninsula Sch Med, Inst Hlth & Care Res, UCL, London
  • ,
  • Morten Gersel Stokholm
  • Derralyn Hughes, UCL, University of London, University College London, Dept Haematol, Inst Immun & Transplantat
  • ,
  • Atul Mehta, UCL, University of London, University College London, Dept Haematol, Inst Immun & Transplantat
  • ,
  • Peter Parbo
  • Rainer Hinz, Univ Manchester, University of Manchester, Wolfson Mol Imaging Ctr
  • ,
  • Nicola Pavese
  • David J. Brooks
  • Anthony H. Schapira, Royal Free Hosp, University of London, University College London, Royal Free London NHS Foundation Trust, UCL Medical School, Lysosomal Storage Dis Unit

BACKGROUND: Glucocerebrosidase gene mutations are a common genetic risk factor for Parkinson's disease. They exhibit incomplete penetrance. The objective of the present study was to measure microglial activation and dopamine integrity in glucocerebrosidase gene mutation carriers without Parkinson's disease compared to controls.

METHODS: We performed PET scans on 9 glucocerebrosidase gene mutation carriers without Parkinson's disease and 29 age-matched controls. We measured microglial activation as 11 C-(R)-PK11195 binding potentials, and dopamine terminal integrity with 18 F-dopa influx constants.

RESULTS: The 11 C-(R)-PK11195 binding potential was increased in the substantia nigra of glucocerebrosidase gene carriers compared with controls (Student t test; right, t = -4.45, P = 0.0001). Statistical parametric mapping also localized significantly increased 11 C-(R)-PK11195 binding potential in the occipital and temporal lobes, cerebellum, hippocampus, and mesencephalon. The degree of hyposmia correlated with nigral 11 C-(R)-PK11195 regional binding potentials (Spearman's rank, P = 0.0066). Mean striatal 18 F-dopa uptake was similar to healthy controls.

CONCLUSIONS: In vivo 11 C-(R)-PK11195 PET imaging detects neuroinflammation in brain regions susceptible to Lewy pathology in glucocerebrosidase gene mutation carriers without Parkinson's. © 2020 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Original languageEnglish
JournalMovement Disorders
Volume36
Issue3
Pages (from-to)774-779
Number of pages6
ISSN0885-3185
DOIs
Publication statusPublished - Mar 2021

Bibliographical note

Publisher Copyright:
© 2020 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society

Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.

    Research areas

  • Parkinson's disease, glucocerebrosidase, microglia, positron emission tomography, substantia nigra

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