Abstract
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 11C-(R)-PK11195 binding potentials, and dopamine terminal integrity with 18F-dopa influx constants. Results: The 11C-(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 11C-(R)-PK11195 binding potential in the occipital and temporal lobes, cerebellum, hippocampus, and mesencephalon. The degree of hyposmia correlated with nigral 11C-(R)-PK11195 regional binding potentials (Spearman's rank, P = 0.0066). 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 glucocerebrosidase gene mutation carriers without Parkinson's.
| Originalsprog | Engelsk |
|---|---|
| Tidsskrift | Movement Disorders |
| Vol/bind | 36 |
| Udgave nummer | 3 |
| Sider (fra-til) | 774-779 |
| ISSN | 0885-3185 |
| DOI | |
| Status | Udgivet - mar. 2021 |
| Udgivet eksternt | Ja |
Bibliografisk note
Funding Information:S.M. has received grant funding from the National Institute of Health Research, the Engineering and Physical Sciences Research Council, and fees for consulting from GLG consulting, Horama and Centogene. D.H. has received fees for research from Sanofi and Takeda, administered through UCL consultants with benefits to research in lysosomal storage diseases. D.B. has received grant funding from Horizon 2020, Danish Council for Independent Research, and Lundbeck Foundation. In the last 12 months A.H.V.S. has received funding from the Medical Research Council, H2020 Parkinson's UK, and the Cure Parkinson Trust. He is an employee of UCL. He has served as a consultant for Prevail Therapeutics. N.P. has received grants funding from the Independent Research Fund Denmark, Danish Parkinson's Disease Association, Parkinson's UK, MRC – Center of Excellence in Neurodegeneration (CoEN) network award, GE Healthcare Grant, Multiple System Atrophy Trust, Weston EU Joint Program Neurodegenerative Disease Research (JPND), EU Horizon 2020 research and innovation program, Italian Ministry of Health, and Honoria for consultancy from Britannia, Boston Scientific, Benevolent AI, and Bial. D.J.B. has received grant funding from the Independent Research Fund Denmark, Lundbeck Foundation, Danish Parkinson's Disease and Alzheimer's Associations, Horizon 2020, and GE Healthcare. M.S., P.P., and A.M. have nothing to disclose.
Publisher Copyright:
© 2020 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society