Parkinson's disease patients frequently have symptoms and signs of autonomic nervous dysfunction that are the source of considerable disability. Recent studies have revealed that most patients with
Parkinson's disease, and all with
Parkinson's disease-associated
orthostatic hypotension, have a loss of cardiac sympathetic innervation. Familial
Parkinson's disease, caused by mutation of the gene encoding
alpha-synuclein, also features
orthostatic hypotension, sympathetic neurocirculatory failure and cardiac
sympathetic denervation. We have recently described a whole-gene triplication of
alpha-synuclein causing
Lewy body parkinsonism in a large, well characterized family called the 'Iowa kindred'. Here we report the results of cardiac PET scanning using the sympathoneural imaging agent, 6-[18F]fluorodopamine in affected and unaffected members of this kindred. Four family members were studied, two with
parkinsonism, one clinically normal and one with
benign essential tremor alone. Both affected members had obvious loss of cardiac sympathetic innervation; the unaffected member had normal innervation, as did the member with isolated
essential tremor. The results indicate that, in this family, where disease is caused by overexpression of normal
alpha-synuclein, cardiac
sympathetic denervation cosegregates with
parkinsonism. Post-mortem studies have demonstrated
synuclein-positive Lewy body formation in the brains of individuals with
parkinsonism who were also in the family described here and who also carry this triplication. These results indicate that both
parkinsonism and cardiac
sympathetic denervation can result from an excess of normal
synuclein.