Clinical and subclinical dopaminergic dysfunction in PARK6-linked parkinsonism: An 18F-dopa PET study
Article first published online: 22 NOV 2002
Copyright © 2002 Wiley-Liss, Inc.
Annals of Neurology
Volume 52, Issue 6, pages 849–853, December 2002
How to Cite
Khan, N. L., Valente, E. M., Bentivoglio, A. R., Wood, N. W., Albanese, A., Brooks, D. J. and Piccini, P. (2002), Clinical and subclinical dopaminergic dysfunction in PARK6-linked parkinsonism: An 18F-dopa PET study. Ann Neurol., 52: 849–853. doi: 10.1002/ana.10417
- Issue published online: 22 NOV 2002
- Article first published online: 22 NOV 2002
- Manuscript Accepted: 3 SEP 2002
- Manuscript Revised: 13 AUG 2002
- Manuscript Received: 28 MAY 2002
- Parkinson's Disease Society. Grant Number: 4000
- Brain Research Trust. Grant Number: 282
PARK6, a locus for early-onset recessive parkinsonism, has been causally implicated in nine unrelated families from four different countries. The gene is still unidentified and hence the importance of PARK6 as a cause of Parkinson's disease is unknown. To date, no pathology or functional imaging studies are available on PARK6-linked parkinsonism. We have used 18F-dopa positron emission tomography to study four patients who are homozygous and three asymptomatic relatives who are heterozygous for PARK6. The clinically affected PARK6 subjects had a similar 85% reduction in posterior dorsal putamen 18F-dopa uptake to a group of idiopathic Parkinson's disease patients matched for clinical disease severity and duration but showed significantly greater involvement of head of caudate and anterior putamen. The group of asymptomatic PARK6 carriers showed a significant mean 20 to 30% reduction in caudate and putamen 18F-dopa uptake in comparison with controls, individual values falling toward the bottom of the normal range. Our results indicate that PARK6 pathology results in a more uniform loss of striatal dopamine terminal function than Parkinson's disease. The subclinical loss of striatal dopamine storage capacity found in the PARK6 carriers implies that the unidentified gene on the short arm of chromosome 1 exhibits either haploinsufficency or a dominant negative effect.