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Updated: Jun 8, 2026
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Metabolic Labeling of Leucine Rich Repeat Kinases 1 and 2 with Radioactive Phosphate
Published on: September 18, 2013
Dopamine turnover increases in asymptomatic LRRK2 mutations carriers.
Vesna Sossi1, Raul de la Fuente-Fernández, Ramachandiran Nandhagopal
1Department of Physics and Astronomy, University of British Columbia, Vancouver British Columbia, Canada. vesna@phas.ubc.ca
Summary
In preclinical Parkinson's disease (PD), dopamine (DA) turnover increases early, independent of dopamine transporter (DAT) levels. This suggests a compensatory mechanism before symptom onset in at-risk individuals.
Area of Science:
- Neuroscience
- Biochemistry
- Medical Imaging
Background:
- Dopamine (DA) turnover increases early in symptomatic Parkinson's disease (PD), linked to the dopamine transporter (DAT).
- Investigating presymptomatic changes in DA turnover and its relationship with other dopaminergic markers is crucial for understanding early PD pathogenesis.
Purpose of the Study:
- To examine changes in DA turnover during the asymptomatic phase of PD.
- To compare these changes with other dopaminergic markers.
- To investigate the relationship between DAT and DA turnover in presymptomatic PD.
Main Methods:
- Positron emission tomography (PET) imaging was used in eight subjects from families with LRRK2 mutations, at increased risk for PD.
- PET tracers included ¹⁸F-fluorodopa (for DA turnover and synthesis/storage), ¹¹C-methylphenidate (for DAT), and ¹¹C-dihydrotetrabenazine (for VMAT2).
- Measurements included effective DA distribution volume (EDV), DA uptake rate K(occ), and binding potentials for DAT (BP(ND_MP)) and VMAT2 (BP(ND_DTBZ)).
Main Results:
- Asymptomatic mutation carriers showed an average 42% reduction in EDV (inverse of DA turnover), a 23% reduction in DAT binding (BP(ND_MP)), and a 17% reduction in VMAT2 binding (BP(ND_DTBZ)).
- DA synthesis and storage marker K(occ) remained within normal ranges.
- Elevated DA turnover was observed in asymptomatic carriers, larger than and independent of changes in other dopaminergic markers, with no correlation between EDV and other markers.
Conclusions:
- Increased DA turnover occurs in presymptomatic carriers at risk for PD, suggesting a compensatory role.
- This compensatory increase in DA turnover is independent of DAT levels in the presymptomatic stage.
- These findings differentiate early presymptomatic PD from the symptomatic phase where DA turnover is related to DAT.
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