Positron emission tomographic analysis of the nigrostriatal dopaminergic system in familial parkinsonism associated with mutations in the parkin gene

Ruediger Hilker, Christine Klein, Mehran Ghaemi, Bernhard Kis, Tim Strotmann, Laurie J. Ozelius, Olaf Lenz, Peter Vieregge, Karl Herholz, Wolf Dieter Heiss*, Peter P. Pramstaller

*Korrespondierende/r Autor/-in für diese Arbeit
203 Zitate (Scopus)

Abstract

A kindred from South Tyrol (northern Italy) with familial, adult-onset parkinsonism of pseudo-dominant inheritance and mutations in the parkin gene was recently described. To gain insight into basal ganglia dysfunction in this form of hereditary parkinsonism, positron emission tomography (PET) with 18-fluorodopa (FDOPA) and 11C-raclopride (RAC) was performed in 5 affected family members and 5 asymptomatic relatives with proven compound heterozygous or heterozygous parkin mutations. Results were compared to findings in healthy control subjects and patients with typical sporadic, idiopathic Parkinson's disease. Similar to findings in the sporadic Parkinson's disease group, presynaptic striatal FDOPA storage was decreased in patients with compound heterozygous parkin mutations, with the most prominent reduction in the posterior part of the putamen. Along with the presynaptic lowered FDOPA uptake, we found a uniform reduction of the striatal 11C-raclopride binding index in all affected family members as compared to asymptomatic family members carrying a heterozygous parkin mutation, sporadic Parkinson's disease, and control subjects. Our PET data provide evidence that parkinsonism in this family is associated with presynaptic dopaminergic dysfunction similar to idiopathic Parkinson's disease pathophysiology, along with alterations at the postsynaptic D2 receptor level. In asymptomatic carriers of a single parkin mutation with an apparently normal allele, we found a mild but statistically significant decrease of mean FDOPA uptake compared to control subjects in all striatal regions. These data indicate a preclinical disease process in these subjects.

OriginalspracheEnglisch
ZeitschriftAnnals of Neurology
Jahrgang49
Ausgabenummer3
Seiten (von - bis)367-376
Seitenumfang10
ISSN0364-5134
DOIs
PublikationsstatusVeröffentlicht - 20.03.2001

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