Imaging dopamine function and microglia in asymptomatic LRRK2 mutation carriers
Morten Gersel Stokholm, Alícia Garrido, Eduardo Tolosa, Mónica Serradell, Álex Iranzo, Karen Østergaard, Per Borghammer, Arne Møller, Peter Parbo, Kristian Stær, David J. Brooks, Marı́a José Martı́, Nicola Pavese
Abstract
Abstract 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.