Imaging dopamine function and microglia in asymptomatic LRRK2 mutation carriers

Neuroinflammation (microglial activation) and subclinical nigrostriatal dysfunction have been reported in subjects at risk of Parkinsonism. Eight non-manifesting carriers (NMCs) of LRRK2 G2019S mutation had 11 C-PK11195 and 18 F-DOPA PET to assess microglial activation and striatal dopamine system i...

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Bibliographic Details
Published in:Journal of neurology 2020-08, Vol.267 (8), p.2296-2300
Main Authors: Gersel Stokholm, Morten, Garrido, Alicia, Tolosa, Eduardo, Serradell, Mónica, Iranzo, Alex, Østergaard, Karen, Borghammer, Per, Møller, Arne, Parbo, Peter, Stær, Kristian, Brooks, David J., Martí, Maria José, Pavese, Nicola
Format: Article
Language:English
Subjects:
Basal ganglia
Brain diseases
Central nervous system diseases
Dihydroxyphenylalanine
Dopamine
Humans
Inflammation
Leucine-Rich Repeat Serine-Threonine Protein Kinase-2 - genetics
LRRK2 protein
Medicine
Medicine & Public Health
Microglia
Movement disorders
Mutation
Mutation - genetics
Neostriatum
Neurology
Neuroradiology
Neurosciences
Original Communication
Parkinson Disease - diagnostic imaging
Parkinson Disease - genetics
Parkinson's disease
Positron emission tomography
Substantia nigra
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Summary:Neuroinflammation (microglial activation) and subclinical nigrostriatal dysfunction have been reported in subjects at risk of Parkinsonism. Eight non-manifesting carriers (NMCs) of LRRK2 G2019S mutation had 11 C-PK11195 and 18 F-DOPA PET to assess microglial activation and striatal dopamine system integrity, respectively. Comparisons were made with healthy controls. Five LRRK2-NMCs had subclinical reductions of putaminal 18 F-DOPA uptake. Three of them had significantly raised nigral 11 C-PK11195 binding bilaterally. These findings indicate that nigrostriatal dysfunction and neuroinflammation occur in LRRK2-NMCs. Studies in larger cohorts with appropriate follow-up are needed to elucidate the significance of neuroinflammation in the premotor phase of LRRK2-PD.
ISSN:0340-5354
1432-1459
DOI:10.1007/s00415-020-09830-3