Alpha-synuclein measures identify progressive neurodegeneration in people with REM sleep behavior disorder

October 1, 2026

SEOUL — Presence of phosphorylated alpha-synuclein (P-SYN) measured in skin biopsies of people with isolated REM sleep behavior disorder (iRBD) could be an early sign of neurodegenerative disease, according to a study released at the International Congress of Parkinson’s Disease and Movement Disorders® in Seoul.

Researchers detected P-SYN in a significant proportion of people with iRBD both at baseline (75%) and at 12-month follow-up (81%), as well as increasing P-SYN levels over that period. Findings strengthen the case of P-SYN as a potential biomarker for indicating who among those with iRBD are at most risk of developing a synucleinopathy, i.e., the phenoconversion rate and for tracking changes in neurodegeneration over time.

iRBD is a strong predictor of synucleinopathies like Parkinson’s disease, multiple system atrophy and dementia with Lewy bodies, however, a robust biomarker for phenoconversion rate is lacking. P-SYN has been investigated as one such promising biomarker, as deposits of P-SYN within the central and peripheral nervous systems can pathologically categorize iRBD. P-SYN can be collected from differing body regions, with skin biopsies being a less invasive route.

Levine and colleagues sought to determine rates and changes of P-SYN in people with confirmed iRBD to determine if it might be used to identify ongoing neurodegeneration. P-SYN was collected from skin biopsies at the distal leg, distal thigh and posterior cervical sites. Their finding that average amounts of P-SYN increased from baseline to follow-up served as a promising first step in this ongoing longitudinal study. 

“This study extends our knowledge of the use of skin P-SYN biomarkers,” said Dr. Roneil Malkani, neurologist at Jesse Brown Veterans Affairs Medical Center and adjunct lecturer at Northwestern University. “While previous studies have shown that skin P-SYN is often positive in people with isolated RBD (likely prodromal synucleinopathy), this study provides longitudinal assessment showing that those who had positive synuclein remain positive, and some of those who were initially negative tested positive on follow-up 12 months later.

“These longitudinal analyses are necessary to help us understand the clinical utility of these tests in the real world and to help plan clinical trials for potential disease-modifying therapies to reduce phenoconversion risk. I hope that, as authors continue the data analysis, we will see how the timing of the skin biopsy tests relate to the timing of RBD onset and phenoconversion to clinical diagnosis of synucleinopathy.”

View the full abstract: The Syn-Sleep Study: Detection of Cutaneous Phosphorylated Alpha-Synuclein in REM Sleep Behavior Disorder. 

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About the 2026 MDS International Congress of Parkinson’s Disease and Movement Disorders^®:
The MDS International Congress is the premier annual event to advance the clinical and scientific discipline of Movement Disorders, including Parkinson’s disease. Convening thousands of leading clinicians, scientists and other health professionals from around the globe, the International Congress will introduce more than 2,000 scientific abstracts and provide a forum for education and collaboration on latest research and treatment findings. 

About the International Parkinson and Movement Disorder Society: 
The International Parkinson and Movement Disorder Society^® (MDS), an international society of more than 12,000 clinicians, scientists, and other healthcare professionals, is dedicated to improving patient care through education and research. For more information about MDS, visit www.movementdisorders.org.