Abstract Details

Title The Syn-sleep Study: Detection of Cutaneous Phosphorylated Alpha-synuclein in REM Sleep Behavior Disorder

Topic Sleep

Presentation(s) P9 - Poster Session 9 (5:00 PM-6:00 PM)

Poster/Presentation
Number 14-001

Objective 1) Determine rates of phosphorylated alpha-synuclein (P-SYN) deposition in idiopathic REM sleep behavior disorder (iRBD) and quantify changes in P-SYN deposition over time. 2) Determine if patterns of P-SYN deposition predict phenoconversion.

Background iRBD is a prodromal neurodegenerative disease characterized by dream reenactment and REM sleep atonia. IRBD is characterized pathologically by the deposition of P-SYN within the central and peripheral nervous systems. iRBD has a high risk of phenoconversion to a clinically apparent synucleinopathy (Parkinson’s disease (PD), multiple system atrophy (MSA), or dementia with Lewy bodies (DLB)), with >73% of patients converting over 12 years.

Design/Methods Patients with a confirmed diagnosis of iRBD (by polysomnography or validated questionnaire and history) were included in this multicenter study. Detailed examinations, orthostatic vital signs, and questionnaires were completed. Medical history, ancillary testing, and polysomnograms (PSG) were reviewed, if applicable. Skin biopsies at the distal leg, distal thigh, and posterior cervical sites were collected. Dual immunohistochemical immunostaining for nerve fibers (protein gene product 9.5) and P-SYN were completed.

Results 80 subjects (31% female) were enrolled. The mean age of the subjects was 67.8±8.7 years. P-SYN was detected in 75% (60/80) of subjects. In a preliminary analysis of the first 33 patients to complete follow-up, there was a significant increase in P-SYN between baseline and 12 months (p=0.04). The average P-SYN composite score at baseline was 4.09±4.99, and at the 12-month follow-up was 5.63±5.87. No complications were noted in the biopsy procedure.

Conclusions Final longitudinal reassessment of these subjects is in progress to determine if P-SYN can serve as a biomarker of disease progression and predict phenoconversion in iRBD patients. Preliminary analysis shows a significant increase in measured cutaneous P-SYN levels between baseline and 12 months. Full follow-up data, including any evidence of phenoconversion, will be presented at the 2026 AAN Meeting.

Authors/Disclosures
Todd D. Levine, MD (Honor Health) PRESENTER	Dr. Levine has received personal compensation for serving as an employee of CND life sciences . Dr. Levine has received personal compensation in the range of $100,000-$499,999 for serving as a Consultant for Nufactor. Dr. Levine has received personal compensation in the range of $50,000-$99,999 for serving as an Expert Witness for PNA. Dr. Levine has or had stock in CND Life Sciences.Dr. Levine has or had stock in Corinthian reference lab.
Bailey Bellaire (CND Life Sciences)	Bailey Bellaire has received personal compensation for serving as an employee of CND Life Sciences.
Sarrah Marcotte	Miss Marcotte has received personal compensation for serving as an employee of CND Life Sciences.
Jourdan Parent, PhD	Dr. Parent has received personal compensation for serving as an employee of CND Life Sciences.
Manuel X. Duval, PhD	Mr. Duval has received personal compensation for serving as an employee of CND Life sciences.
Roy L. Freeman, MD (Beth Israel Deaconess Hosp)	Dr. Freeman has received personal compensation in the range of $50,000-$99,999 for serving as a Consultant for Cutaneous Diagnostic Life Sciences. Dr. Freeman has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Vertex. Dr. Freeman has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant 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. 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. Dr. Freeman has received research support from Regeneron.
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 or had stock in CND Life Sciences.Dr. Gibbons has received publishing royalties from a publication relating to health care.

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