Skin-biopsy synuclein (Syn-One)

The research record

This is the project's file for this landmark, as written and checked. Sources are listed at the end; anything not yet confirmed is marked "Not yet verified".

Who

Christopher Gibbons, Levine, Roy Freeman and colleagues (32 authors) at 30 US neurology sites. The paper lists grants from the US National Institute of Neurological Disorders and Stroke (a small-business grant, R44 NS117214) and the National Institute on Aging. The test is sold by CND Life Sciences: the disclosures say Gibbons holds stock options in the company and Levine has a pending patent on the method, and Alzforum commentator Thomas Beach adds that both slide readers are CND founders.

What happened

Gibbons et al. (JAMA, 16 April 2024, vol 331, pp 1298–1306; online 20 March) enrolled 428 people; 343 entered the main analysis (223 with a synucleinopathy, 120 controls) after an expert panel reviewed diagnoses. Three 3 mm skin punches (neck, knee, ankle) were stained for synuclein phosphorylated at serine 129 inside nerve fibres. Positive in 92.7% (89 of 96) of Parkinson's, 98.2% of multiple system atrophy, 96.0% of dementia with Lewy bodies and 100% of pure autonomic failure, versus 3.3% (4 of 120) of controls. No serious complications were reported.

Why it moved us toward a cure

Trials need a way to confirm the target is present. This is the skin version of the marker in landmark 94, and a simpler alternative to the spinal-fluid seed amplification assay.

Earlier gut biopsies for synuclein had promised much but lacked specificity (landmark 261).

Outcome

Open. Alzforum commentators raised concerns: the reference diagnosis was clinical (itself imperfect), controls were younger (median 59), early and prodromal disease and look-alike disorders were not tested, there was no third-party blinding, and Beach cited the Foundation-sponsored S4 study, which reported only 24.1% sensitivity (100% specificity). Others were more positive (Hansson). The paper itself calls for validation in unselected clinical populations. A 2026 expert panel proposed a standard protocol for the stain (Molecular Neurodegeneration, DOI 10.1186/s13024-026-00966-w; abstract-level only).

Sources

• Gibbons et al., JAMA 2024, DOI 10.1001/jama.2024.0792, PMID 38506839 (no correction or retraction listed; one letter exchange, JAMA 27 Aug 2024) · NIH Research Matters
• Alzforum commentary
• Not yet verified: the S4 study's own paper and method; the test's current clinical availability and price; whether any independent replication of the 92.7% figure exists.