GUIDANCE FOR USE
The Syn-One Test® is an anatomical pathology test to aid in the evaluation of patients with clinical features suggestive of a neurodegenerative disease. The test utilizes immunofluorescence techniques to detect and quantify phosphorylated alpha-synuclein (P-SYN) in cutaneous nerves and to assess intraepidermal nerve fiber density (IENFD). Histopathologic evaluation with hematoxylin and eosin (H&E) is performed to diagnose dermatologic conditions. Congo red staining is ordered to diagnose amyloidosis. Results should be interpreted in conjunction with the patient’s medical history and clinical presentation.
Stability of tissue specimens in fixative beyond 120 hours has not been established. Prolonged fixation may affect detection of phosphorylated alpha-synuclein and measurement of intraepidermal nerve fiber density.
This test was developed and its performance characteristics determined by CND Life Sciences, Inc. It has not been cleared or approved by the U.S. Food and Drug Administration. CND Life Sciences, Inc. is accredited by the College of American Pathologists (CAP), holds a CLIA Certificate of Accreditation to perform high-complexity testing, and holds a Clinical Laboratory Evaluation Program (CLEP) permit from New York.
Please visit our website for additional relevant scientific publications
References
For additional information on the skin biopsy technique and detection of phosphorylated alpha-synuclein see:
Gibbons CH, Levine T, Adler C, et al. Skin biopsy detection of phosphorylated α-synuclein in patients with synucleinopathies. JAMA. Published online March 20, 2024. doi:10.1001/jama.2024.0792
Gibbons C, Wang N, Rajan S, et al. Cutaneous α-synuclein signatures in patients with multiple system atrophy and Parkinson disease. Neurology.2023; 100(15), e1529–e1539. doi: 10.1212/WNL.0000000000206772
Kim JY, Illigens BM, McCormick MP, Wang N, Gibbons CH. Alpha-synuclein in skin nerve fibers as a biomarker for alpha-synucleinopathies. J Clin Neurol. 2019 Apr;15(2):135-142. doi: 10.3988/jcn.2019.15.2.135
Gibbons CH, Garcia J, Wang N, Shih LC, Freeman R. The diagnostic discrimination of cutaneous α-synuclein deposition in Parkinson disease. Neurology. 2016 Aug 2;87(5):505-12. doi: 10.1212/WNL.0000000000002919
Provitera V, Gibbons CH, Wendelschafer-Crabb G, et al. A multi-center, multinational age- and gender-adjusted normative dataset for immunofluorescent intraepidermal nerve fiber density at the distal leg. Eur J Neurol. 2016 Feb;23(2):333-8. doi: 10.1111/ene.12842
Rawls A, Okun MS. Parkinson Disease. Continuum (Minneap Minn). 2025 Aug;31(4):930-955. doi: 10.1212/cont.0000000000001593. Epub 2025 Aug 1. PMID: 40748114.
Gummerson CE, Tinaz S, Santini V, Zubair A. Utilization of Skin Punch Biopsy for the Diagnosis of α-Synucleinopathy in Clinical Practice. Mov Disord Clin Pract. 2026 Jan;13(1):191-197. doi: 10.1002/mdc3.70272. Epub 2025 Aug 5. PMID: 40762364; PMCID: PMC12839503
Nandanwar D, Truong DD. Multiple system atrophy: Diagnostic challenges and a proposed diagnostic algorithm. Clin Park Relat Disord. 2024 Sep 18;11:100271.
Furia A, Incensi A, Delprete C, Rizzo G, Bonvegna S, Piatti M, Olivola E, Ventruto F, Vacchiano V, Fileccia E, Cilia R, Modugno N, Liguori R, Donadio V. Identification of Dementia With Lewy Bodies by Skin Biopsy in Recent-Onset Cognitive Impairment. Ann Clin Transl Neurol. 2025 Aug 5.
Isaacson JR, Freeman R and Gibbons CH (2024) Clinical utility of synuclein skin biopsy in the diagnosis and evaluation of synucleinopathies. Front. Neurol. 15:1510796. doi: 10.3389/fneur.2024.1510796.
Anis S, Kundrick A, et al. Phosphorylated alpha-synuclein skin biopsy alters diagnosis in two out of three patients: Initial findings in a tertiary center. Parkinsonism Relat Disord. 2026;145:108234. doi:10.1016/j.parkreldis.2026.108234.
