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Updated: Dec 23, 2025

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Imaging dopamine function and microglia in asymptomatic LRRK2 mutation carriers.

Morten Gersel Stokholm1, Alicia Garrido2,3, Eduardo Tolosa2,3,4

  • 1Department of Nuclear Medicine and PET Centre, Aarhus University Hospital, Noerrebrogade 44, bldg. 10G, 8000, Aarhus C, Denmark.

Journal of Neurology
|April 23, 2020
PubMed
Summary

Early Parkinsonism signs, including neuroinflammation and nigrostriatal dysfunction, are present in LRRK2 G2019S mutation carriers before symptoms manifest. These preclinical changes suggest potential therapeutic targets for LRRK2-related Parkinson's disease.

Keywords:
Clinical neurologyGeneticsMovement disordersPETParkinson’s disease

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Area of Science:

  • Neuroscience
  • Neurology
  • Genetics

Background:

  • Neuroinflammation, characterized by microglial activation, and subclinical nigrostriatal dysfunction are observed in individuals at risk for Parkinsonism.
  • The LRRK2 G2019S mutation is a common genetic factor associated with an increased risk of developing Parkinson's disease.

Purpose of the Study:

  • To investigate early neuroinflammation and nigrostriatal dopaminergic system integrity in non-manifesting carriers (NMCs) of the LRRK2 G2019S mutation.
  • To assess the presence of subclinical markers of Parkinsonism in individuals who carry the LRRK2 G2019S mutation but do not yet show symptoms.

Main Methods:

  • Eight non-manifesting carriers (NMCs) of the LRRK2 G2019S mutation underwent Positron Emission Tomography (PET) scans.
  • 11C-PK11195 PET was used to assess microglial activation (neuroinflammation).
  • 18F-DOPA PET was employed to evaluate striatal dopamine system integrity, comparing results with healthy controls.

Main Results:

  • Five LRRK2-NMCs exhibited subclinical reductions in putaminal 18F-DOPA uptake, indicating nigrostriatal dysfunction.
  • Three of these individuals showed significantly elevated nigral 11C-PK11195 binding bilaterally, suggesting neuroinflammation.
  • These findings demonstrate concurrent nigrostriatal dysfunction and neuroinflammation in pre-symptomatic LRRK2 mutation carriers.

Conclusions:

  • Neuroinflammation and nigrostriatal dysfunction are detectable in the premotor phase of LRRK2-related Parkinson's disease.
  • Further research in larger cohorts with long-term follow-up is necessary to understand the prognostic significance of these preclinical changes.