Abstract Details

Title Cutaneous ?-Synuclein Is a Biomarker of Parkinson Disease Severity

Topic Autonomic Disorders

Presentation(s) S37 - (-)

Poster/Presentation
Number 002

Background Parkinson disease is a multisystem neurodegenerative disease with deposition of ?-synuclein in the central, peripheral and enteric nervous systems. The most prominent manifestations of Parkinson disease are due to central, motor system neurodegeneration but there is also widespread peripheral, autonomic and enteric nervous system degeneration with associated clinical features.

Objective

Design/Methods Twenty patients with Parkinson disease and 14 age and gender matched control subjects underwent examinations, autonomic testing and skin biopsies at the distal leg, distal thigh and proximal thigh. Skin biopsies were stained for PGP9.5, tyrosine hydroxylase, vasoactive intestinal peptide and ?-synuclein. The density of intra-epidermal, sudomotor and pilomotor nerve fibers was calculated and the ratio of ?-synuclein to nerve innervation (?-synuclein ratio). Results were compared to exam scores and autonomic function testing.

Results Patients with Parkinson disease had a distal sensory and autonomic neuropathy characterized by loss of intra-epidermal and pilomotor fibers (P<0.05 vs. controls, all sites) but no difference in sudomotor innervation. Patients with Parkinson disease had higher ?-synuclein ratios compared to controls within pilomotor nerves and sudomotor nerves at all sites (P<0.01, all sites). Higher ?-synuclein ratios correlated with the fall in systolic blood pressure on tilt (r=-0.55, P<0.01), the Hoehn and Yahr scores (r=0.38, P<0.05) and with heart rate variability during paced breathing (r=-0.65, P>0.01). Alpha-synuclein ratios were not increased within sensory nerve fibers.

Conclusions Alpha-synuclein ratios are elevated within sympathetic adrenergic and sympathetic cholinergic fibers, but not sensory fibers, of patients with Parkinson disease. Higher ?-synuclein ratios are associated with greater autonomic dysfunction and more advanced Parkinson disease. These data suggest that the ?-synuclein ratio may be a useful biomarker in patients with Parkinson disease.

Authors/Disclosures
Ningshan Wang, MD, PhD (BIDMC) PRESENTER	Dr. Wang has nothing to disclose.
Douglas L. Arnold, MD, FAAN (Montreal Neurological Institute, McGill Univ)	Dr. Arnold has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Biogen. Dr. Arnold has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for BMS. Dr. Arnold has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Frequency Therapeutics. Dr. Arnold has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Merck. Dr. Arnold has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Novartis. Dr. Arnold has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Roche. Dr. Arnold has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Sanofi. Dr. Arnold has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Shionogi. Dr. Arnold has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Xfacto communications. Dr. Arnold has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Eli Lilly. Dr. Arnold has received personal compensation in the range of $500-$4,999 for serving as a Consultant for EMD Serono. Dr. Arnold has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biohaven. Dr. Arnold has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Find therapeutics. Dr. Arnold has received personal compensation in the range of $500-$4,999 for serving as a Consultant for GSK. Dr. Arnold has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Idorsia. Dr. Arnold has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Kiniksa. Dr. Arnold has stock in NeuroRx.
Roy L. Freeman, MD (Beth Israel Deaconess Hosp)	Dr. Freeman has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Regenacy. Dr. Freeman has received personal compensation in the range of $100,000-$499,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Neurobo. Dr. Freeman has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Vertex. Dr. Freeman has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Eli-Lilly. Dr. Freeman has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Theravance. Dr. Freeman has received personal compensation in the range of $10,000-$49,999 for serving as an officer or member of the Board of Directors for Inhibikase. Dr. Freeman has received personal compensation in the range of $10,000-$49,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Elsevier. Dr. Freeman has stock in Neurobo. Dr. Freeman has stock in Cutaneous NeuroDiagnostics. The institution of Dr. Freeman has received research support from NIH. The institution of Dr. Freeman has received research support from Theravance. The institution of Dr. Freeman has received research support from Biohaven. The institution of Dr. Freeman has received research support from Lundbeck.
Christopher H. Gibbons, MD, FAAN (Beth Israel Deaconess Medical Center)	Dr. Gibbons has received personal compensation for serving as an employee of CND Life Sciences. Dr. Gibbons has stock in CND Life Sciences. Dr. Gibbons has received publishing royalties from a publication relating to health care. Dr. Gibbons has received personal compensation in the range of $5,000-$9,999 for serving as a Expert Advisor with Department of Justice.

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