PET studies of parkinsonism associated with mutation in the alpha-synuclein gene.
OBJECTIVE
To assess the pattern of dopaminergic abnormalities in a Greek-American kindred (family H) with autosomal dominantly inherited, levodopa-responsive parkinsonism caused by a mutation of the gene encoding alpha-synuclein.


BACKGROUND
Mutations of alpha-synuclein have been associated recently with dominantly inherited, levodopa-responsive parkinsonism. The pattern of dopamine deficiency and status of postsynaptic dopamine receptors in this condition have not been reported previously. The authors followed a large, six-generation family in whom the affected members carry the recently reported G209A mutation in the gene encoding alpha-synuclein.


METHODS
The authors studied four affected and two clinically unaffected gene-negative members of family H using [18F]-6-fluoro-L-dopa (FD) and [11C]-raclopride (RAC) PET to assess presynaptic dopaminergic function and dopamine D2 receptors. The results were compared with normal subjects and patients with sporadic, idiopathic PD (IP).


RESULTS
In affected individuals, FD uptake was reduced in both the caudate and the putamen, but the putamen was affected more severely than the caudate, as seen in IP. RAC binding was within the normal range, but the ratio of RAC binding in the putamen to that in the caudate was increased in affected members of family H. This pattern is similar to that seen in IP.


CONCLUSIONS
PET of the nigrostriatal system in parkinsonism associated with a mutation in the ac-synuclein gene indicates that it results in a pattern of dopamine deficiency, with preserved D2 binding, indistinguishable from IP.
Samii
A
A
Neurodegenerative Disorders Centre, Vancouver Hospital and Health Sciences Centre, British Columbia, Canada.
Markopoulou
K
K
Wszolek
Z K
ZK
Sossi
V
V
Dobko
T
T
Mak
E
E
Calne
D B
DB
Stoessl
A J
AJ
D000328:Adult; D000978:Antiparkinson Agents / Q000008:administration & dosage / Q000009:adverse effects; D001931:Brain Mapping; D002421:Caudate Nucleus / Q000000981:diagnostic imaging; D002869:Chromosome Aberrations / Q000235:genetics; D025063:Chromosome Disorders; D005260:Female; D015870:Gene Expression / Q000502:physiology; D005799:Genes, Dominant / Q000235:genetics; D006115:Greece / Q000208:ethnology; D006801:Humans; D007980:Levodopa / Q000008:administration & dosage / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000235:genetics*; D010300:Parkinson Disease / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000235:genetics*; D010375:Pedigree; D010750:Phosphoproteins / Q000235:genetics*; D011699:Putamen / Q000000981:diagnostic imaging; D011954:Receptors, Dopamine / Q000235:genetics; D051843:Synucleins; D014055:Tomography, Emission-Computed; D014481:United States; D051844:alpha-Synuclein
D000978:Antiparkinson Agents; D009419:Nerve Tissue Proteins; D010750:Phosphoproteins; D011954:Receptors, Dopamine; C497604:SNCA protein, human; D051843:Synucleins; D051844:alpha-Synuclein; D007980:Levodopa