Imaging dopamine function and microglia in asymptomatic LRRK2 mutation carriers

J Neurol. 2020 Aug;267(8):2296-2300. doi: 10.1007/s00415-020-09830-3. Epub 2020 Apr 21.

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 11C-PK11195 and 18F-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 18F-DOPA uptake. Three of them had significantly raised nigral 11C-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.

Keywords: Clinical neurology; Genetics; Movement disorders; PET; Parkinson’s disease.

MeSH terms

  • Dopamine*
  • Humans
  • Leucine-Rich Repeat Serine-Threonine Protein Kinase-2 / genetics
  • Microglia
  • Mutation / genetics
  • Parkinson Disease* / diagnostic imaging
  • Parkinson Disease* / genetics

Substances

  • LRRK2 protein, human
  • Leucine-Rich Repeat Serine-Threonine Protein Kinase-2
  • Dopamine