Skin Biopsy Detects Synuclein Pathology in 75% of Those with Idiopathic REM Sleep Behavior Disorder

According to study results presented at the 2025 Annual Meeting of the Associated Professional Sleep Societies (APSS), 75% of people with idiopathic rapid eye movement (REM) sleep behavior disorder (iRBD) and no evidence of other neurodegenerative disease tested positive for cutaneous phosphorylated α-synuclein deposition on skin biopsy. According to a press release from CND Life Sciences (Scottsdale, AZ), a company that develops neurodiagnostic biomarker testing technology, the baseline results from the ongoing Syn-Sleep Study (NCT05757206) suggest that phosphorylated α-synuclein biomarker testing may have potential applications for early intervention to prevent disease progression to Parkinson disease (PD) or dementia with Lewy bodies (DLB).

The Syn-Sleep Study is a National Institutes of Health (NIH)–funded, 24-month, multicenter, prospective trial assessing whether the presence and pattern of phosphorylated α-synuclein deposition in skin biopsies can predict eventual progression to clinically definite synucleinopathy, such as PD, DLB, and multiple system atrophy (MSA). Conducted across 11 sites in the United States, the study population includes 80 people with iRBD, all without a current diagnosis of other neurodegenerative diseases. At baseline, the participants, who had experienced an average of 6.7 years of symptoms of iRBD, were assessed for cutaneous phosphorylated α-synuclein deposition using a skin biopsy test

• 75% of patients tested positive for cutaneous phosphorylated α-synuclein at baseline
• Participants who tested positive for baseline phosphorylated α-synuclein were more likely to be older, have a longer iRBD symptom duration, and have a greater degree of hyposmia
• Symptom severity, autonomic symptom, and iRBD diagnostic methodology (polysomnography vs questionnaire) did not result in different phosphorylated α-synuclein positivity rates

“We are currently doing a longitudinal reassessment of these subjects to determine if quantification of [phosphorylated α-synuclein] can serve as a biomarker of disease progression,” said Todd Levine, MD, Chief Medical Officer of CND Life Sciences and principle investigator of the study. “The ability to detect those patients at risk opens the door for earlier disease modulation and prevention trials.”