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Abstract Details

Cutaneous Alpha-Synuclein Deposition Across the Synucleinopathies
Movement Disorders
S17 - Parkinson's Disease Biomarkers and Pathophysiology (1:48 PM-2:00 PM)
005
To define the cutaneous deposition of phosphorylated alpha-synuclein in synucleinopathies.
We have previously reported that α-synuclein can be detected within cutaneous nerve fibers of patients with Parkinson’s disease (PD) and multiple system atrophy (MSA).  We now report the deposition of phosphorylated alpha-synuclein in all forms of synucleinopathy including PD, MSA, dementia with Lewy bodies (DLB) and pure autonomic failure (PAF). 
88 patients with synucleinopathy, 44 healthy control and 29 control subjects with concomitant disease (diabetic neuropathy, stroke, Alzheimer’s disease) had detailed neurological examinations and autonomic function testing. Skin biopsies were taken from the posterior cervical, proximal and distal thigh, and were stained for PGP9.5 and phosphorylated alpha-synuclein. 

Phosphorylated alpha-synuclein was detected in 41/42 patients with PD, 17/17 with MSA, 14/14 with DLB, 14/15 with PAF, 0/44 healthy controls and 0/29 disease controls.  98% of synucleinopathy patients were positive in 1 or more biopsies, and none of the healthy or disease controls were positive.  Moderate correlations were noted between disease duration, disease severity (as measured by validated scales) and phosphorylated synuclein deposition (correlations 0.42-0.61, P<0.01).
We report the largest study of cutaneous phosphorylated alpha synuclein detection in patients with all forms of synucleinopathy.  Results were similar across the various clinical synucleinopathy phenotypes and demonstrated a clinical correlation with quantified examination scores.  These results carry significant implications for disease diagnosis, prognosis and therapeutic interventions that alter the natural history of the disease.  
Authors/Disclosures
Christopher H. Gibbons, MD, FAAN (Beth Israel Deaconess Medical Center)
PRESENTER 		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.
Ningshan Wang, MD, PhD (BIDMC) Dr. Wang has nothing to disclose.
Sharika Rajan, MD (NIH) Dr. Rajan has nothing to disclose.
Drew S. Kern, MD, FAAN (University of Colorado) Dr. Kern has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Medtronic. The institution of Dr. Kern has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Boston Scientific. The institution of Dr. Kern has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Abbvie. Dr. Kern has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Abbott. The institution of Dr. Kern has received research support from Boston Scientific. The institution of Dr. Kern has received research support from AbbVie Pharmaceticals. Dr. Kern has received research support from Medtronic.
Jose-Alberto Palma, MD, PhD, FAAN (New York University Grossman School of Medicine) Dr. Palma has received personal compensation for serving as an employee of Novartis. Dr. Palma 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 Clinical Autonomic Research. The institution of Dr. Palma has received research support from National Institutes of Health. Dr. Palma has received publishing royalties from a publication relating to health care.
Horacio C. Kaufmann, MD, FAAN (NYU Langone Health - NYU Dysautonomia Center) Dr. Kaufmann has received personal compensation in the range of $50,000-$99,999 for serving as a Consultant for Theravance. Dr. Kaufmann has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Parexel. Dr. Kaufmann has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Teva Pharmaceuticals. Dr. Kaufmann has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Curasen Therapeutics. Dr. Kaufmann has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Lundbeck. Dr. Kaufmann has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Takeda Pharmaceuticals. Dr. Kaufmann has received personal compensation in the range of $5,000-$9,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Spinger. The institution of Dr. Kaufmann has received research support from Biogen. The institution of Dr. Kaufmann has received research support from Vaxxinity. Dr. Kaufmann has received publishing royalties from a publication relating to health care.
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.