Brain Advance Access originally published online on January 21, 2004
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Brain, Vol. 127, No. 4, 768-772, 2004
© 2004 Guarantors of Brain
doi: 10.1093/brain/awh081
Association between cardiac denervation and parkinsonism caused by 
-synuclein gene triplication
1 Parkinson’s Unit, Neurogenetics Branch, 2 Clinical Neurocardiology Section, National Institute of Neurological Disorders and Stroke and 3 Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA
Correspondence to: Katrina Gwinn-Hardy, MD, 6001 Executive Blvd., NSC 2142, Bethesda, MD 20892, USA E-mail: gwinnk{at}ninds.nih.gov
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 
-synuclein, also features orthostatic hypotension, sympathetic neurocirculatory failure and cardiac sympathetic denervation. We have recently described a whole-gene triplication of -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 -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.
Key Words: fluorodopamine; norepinephrine; orthostatic hypotension; alpha-synuclein; baroreflex
Received August 14, 2003. Revised November 16, 2003. Accepted November 23, 2003.
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