Category: Parkinson's Disease (Other)
Objective: The goals of this study are to 1) determine rates of phosphorylated alpha-synuclein (P-SYN) deposition in iRBD, 2) quantify changes in P-SYN deposition over time, and 3) determine if patterns of P-SYN deposition predict phenoconversion.
Background: Isolated REM sleep behavior disorder (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.
Method: Patients with a confirmed diagnosis of RBD (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. 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: Eighty subjects (67.8±8.7 years, 31% female) were enrolled at baseline. P-SYN was detected in 75% (60/80) of subjects at baseline. Seventy subjects (68.2±8.5 years, 29% female) completed the 12-month follow-up, representing 87.5% of the originally enrolled. P-SYN was detected in 81.4% (57/70) of subjects at follow-up (all P-SYN positive cases at baseline were positive at follow-up). The average P-SYN composite score at baseline was 3.85±4.28, and at the 12-month follow-up was 5.41±5.29 (p<0.01). Of the P-SYN negative cases at baseline, 4/70 (5.71%) were P-SYN positive at follow-up. No complications were noted in the biopsy procedure.
Conclusion: P-SYN is detected in the majority of individuals with RBD. There is a significant increase in P-SYN levels over 12 months. Further 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.
To cite this abstract in AMA style:
T. Levine, S. Marcotte, J. Parent, B. Bellaire, M. Duval, R. Freeman, C. Gibbons. The Syn-Sleep Study: Detection of Cutaneous Phosphorylated Alpha-Synuclein in REM Sleep Behavior Disorder [abstract]. Mov Disord. 2026; 41 (suppl 1). https://www.mdsabstracts.org/abstract/the-syn-sleep-study-detection-of-cutaneous-phosphorylated-alpha-synuclein-in-rem-sleep-behavior-disorder-2/. Accessed October 1, 2026.« Back to 2026 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/the-syn-sleep-study-detection-of-cutaneous-phosphorylated-alpha-synuclein-in-rem-sleep-behavior-disorder-2/