Skin Biopsy Test Detects Neurodegenerative Biomarker in 75% of REM Sleep Disorder Patients
核心洞察
The Syn-One Test (搜索) successfully detected phosphorylated alpha-synuclein (搜索) in skin biopsies of 75% of patients with idiopathic REM sleep behavior disorder (搜索), closely mirroring the 73.5% conversion rate to neurodegenerative diseases within 12 years.
The NIH-sponsored Syn-Sleep Study enrolled 80 participants across 11 U.S. sites, with P-SYN positive individuals tending to be older and having longer duration of symptoms compared to negative participants.
This minimally invasive diagnostic approach could enable early detection of synucleinopathies (搜索) like Parkinson's disease (搜索), dementia with Lewy bodies (搜索), and multiple system atrophy (搜索) up to a decade before clinical symptoms emerge.
A new diagnostic test has successfully detected a key neurodegenerative biomarker in 75% of patients with idiopathic REM sleep behavior disorder (搜索) (iRBD), offering potential for early identification of individuals at risk for developing Parkinson's disease (搜索) and related conditions. The findings from the NIH-sponsored Syn-Sleep Study were presented at SLEEP 2025, the 39th annual meeting of the Associated Professional Sleep Societies.
The Syn-One Test (搜索), developed by CND Life Sciences (搜索), uses a simple in-office skin punch biopsy to detect phosphorylated alpha-synuclein (搜索) (P-SYN), a pathological protein associated with neurodegenerative conditions known as synucleinopathies (搜索). These include Parkinson's disease (搜索) (PD), dementia with Lewy bodies (搜索) (DLB), and multiple system atrophy (搜索) (MSA).
Study Design and Participants
The 24-month longitudinal study enrolled 80 participants with confirmed iRBD across 11 sites in the United States. Participants had a mean age of 67.8±8.9 years and had experienced iRBD symptoms for an average of 6.7 years. The diagnosis of iRBD was confirmed either through the REM Sleep Disorder Screening Questionnaire (47 participants) or by polysomnogram (33 participants).
iRBD is a sleep disorder that causes affected individuals to act out their dreams, often with violent movements and vocalizations. Patients may kick, punch, jump out of bed, and yell in their sleep. The condition is considered "idiopathic" when there is no clear cause for the symptoms.
Key Findings
At baseline evaluation, 60 of 80 participants tested positive for P-SYN on at least one of three skin biopsy locations taken from the distal leg, distal thigh, and posterior cervical region. The 75% detection rate closely mirrors previous longitudinal data showing that 73.5% of patients diagnosed with iRBD convert to PD, DLB, or MSA within 12 years.
Participants who tested positive for P-SYN demonstrated distinct characteristics compared to those who tested negative. P-SYN positive individuals were older (68.7 vs. 65.1 years) and had experienced longer duration of iRBD symptoms (6.8 vs. 6.2 years). Additionally, those with P-SYN found in skin biopsy tended to have a greater degree of hyposmia (搜索), a reduced ability to smell.
Notably, P-SYN positivity rates did not differ based on the severity of iRBD symptoms, autonomic symptoms, or how iRBD was diagnosed. This finding suggests that even patients with milder or atypical presentations may harbor significant disease risk.
Clinical Implications
"These results support evidence that iRBD is a prodromal neurodegenerative condition and suggests that a minimally invasive skin biopsy can be used to assess P-SYN status in these patients," said Michele Tagliati, MD, a movement specialist in the Department of Neurology at Cedars-Sinai in Los Angeles and one of the study's investigators. "As the field advances and there are lifestyle interventions and future drug therapies that could address diseases like PD and DLB before they fully develop, determining if an RBD patient has synuclein deposition will be increasingly important."
The Syn-One Test (搜索) has previously demonstrated a 95% positivity rate in patients with clinically definite synucleinopathies (搜索) including PD, DLB, and MSA. The test analyzes three small skin biopsy samples collected through an in-office procedure and includes an assessment of intraepidermal nerve fiber density and other important pathologic markers.
Future Research Directions
"We are currently doing a longitudinal reassessment of these subjects to determine if quantification of P-SYN can serve as a biomarker of disease progression," said Todd Levine, MD, chief medical officer of CND Life Sciences (搜索) and principal investigator of the study. "The ability to detect those patients at risk opens the door for earlier disease modulation and prevention trials."
The researchers hypothesize that enrolled individuals with greater P-SYN burden are likely to progress to higher intensity neurodegenerative conditions. The test may be able to detect this problem a decade or more before clinical symptoms of a synucleinopathy emerge, potentially facilitating lifestyle changes, clinical monitoring, and inclusion in disease prevention trials.
Diagnostic Utility
The Syn-One Test (搜索) provides a way to distinguish patients with underlying alpha-synuclein (搜索) pathology from those with other etiologies of RBD, helping to refine diagnosis, guide prognosis, and tailor management. Not all patients with iRBD will progress to neurodegenerative disease, as some have reversible or non-neurodegenerative causes.
No adverse events were reported as a result of the skin biopsy procedure, and the test's simplicity and tolerability make it well-suited for routine use in outpatient settings. More than 3,000 neurologists and other clinicians in 50 states have used the Syn-One Test (搜索) to support their diagnostic evaluation of patients.
The study represents a significant step toward proactive, personalized neurology care, potentially enabling earlier intervention and better outcomes for patients at risk of developing neurodegenerative diseases.