Studies in Clinical Utility of Skin Biopsy-Based Testing in Synucleinopathies
Prominent Academic Centers Present Findings at the 2025 MDS Congress
Research supporting the clinical utility of the Syn-One Test was featured by multiple academic centers in poster presentations at the most recent The International Congress of Parkinson’s Disease and Movement Disorders® held in Hawaii. These studies further the clinical evidence published by groups from Beth Israel Deaconess Medical Center and Yale New Haven Health System.1,2 This work highlights how skin biopsy-based biomarkers can be incorporated into the clinical evaluations of synucleinopathies when the clinical presentation is unclear, aligning with the diagnostic workflow outlined in the recent Continuum review.3
Five academic centers presented research at this year’s Congress in which skin biopsy results confirmed, refined, or changed initial diagnoses, noting its potential to resolve uncertainty in parkinsonian syndromes and related conditions: Cedars-Sinai Medical Center, Vanderbilt University Medical Center, the Medical University of South Carolina, the Cleveland Clinic, and the University of Texas Health Science Center at Houston.
Cedars-Sinai investigators highlighted examples of diagnostic mismatches, driving the need for multimodal integration, describing “the importance of using a combination of clinical assessment, imaging and immunohistochemical biomarkers to achieve a precise diagnosis of cases presenting as parkinsonism.”4
Vanderbilt University and Medical University of South Carolina researchers emphasized real-world applications of skin biopsy testing for P-SYN in providing “clinically meaningful data in the diagnosis of synucleinopathies,” leading to a change in diagnosis in nearly one out of three cases.5
The Cleveland Clinic researchers described the utilization patterns of skin biopsy for P-SYN and its impact on patient management, finding that the tests “contribute significantly to the diagnosis and management of patients with suspected synucleinopathies, with results solidifying the diagnosis and influencing management in the majority of cases.” Biopsy results helped solidify the diagnoses in 88.2% of cases and influenced management in 73.0% of the 56 cases referred for a P-SYN skin biopsy in 2024 at the Cleveland Clinic Center.6
The University of Texas Health Science Center at Houston went beyond purely confirming presence of P-SYN in suspected parkinsonism cases, including biopsy pattern analysis in their study, demonstrating the value of regional distribution of pathology in distinguishing PD, MSA, and DLB. These findings build on the emerging concept that cutaneous pathological signatures can help with differential diagnosis. This is an evolving diagnostic dimension for synucleinopathies first introduced in 2023 in Neurology, “Cutaneous α-Synuclein Signatures in Patients With Multiple System Atrophy and Parkinson Disease.”7 The authors reflect that the “presence of P-SYN and its deposition pattern on skin biopsy may be utilized to confirm a suspected diagnosis of PD, DLB, or MSA, while absence of P-SYN deposition may be used to distinguish between synucleinopathy mimics such as secondary parkinsonism or PSP.” The authors concluded that skin biopsy for P-SYN played a role in providing a specific diagnosis in 23 of 25 (92%) of patients “without the need for invasive procedures.”8
The research from these prominent academic centers suggests an important theme for clinical practice: phosphorylated alpha-synuclein detection through a simple skin biopsy is a valuable and validated biomarker in the diagnosis of synucleinopathies. Collectively, these findings continue to strengthen the case supporting the role of skin biopsy-based biomarkers in diagnostic workflows for synucleinopathies, helping to enhance diagnostic precision and clinical confidence when presentations are unclear.
References
1Gummerson 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. Published online August 5, 2025. doi:10.1002/mdc3.70272
2Isaacson JR, Freeman R, Gibbons CH. Clinical utility of synuclein skin biopsy in the diagnosis and evaluation of synucleinopathies. Front Neurol. 2024;15:1510796. Published 2024 Dec 18. doi:10.3389/fneur.2024.1510796
3Rawls AE, Okun MS. Parkinson Disease. Continuum (Minneap Minn). 2025;31(4):930-955. doi:10.1212/cont.0000000000001593.
4Gomez A, Malatt C, Hogg E, et al. Diagnostic mismatches between clinical assessment, imaging and alpha-synuclein biomarkers in parkinsonian syndromes [abstract]. Mov Disord. 2025; 40 (suppl 1).
5Yu C, Cooper C. Real world application of alpha-synuclein skin biopsy in the diagnosis of synucleinopathies at a tertiary care center [abstract]. Mov Disord. 2025; 40 (suppl 1) (32.95%, N=27/82).
6Anis S, Kundrick A, Piccinin C, et al. Utilization of Phosphorylated Alpha-Synuclein Skin Biopsy Testing in a Movement Disorders Center [abstract]. Mov Disord. 2025; 40 (suppl 1).
7Gibbons 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.
8Chen M, Christie M. Impact of Skin Biopsy Detection of Phosphorylated Alpha-Synuclein and its Distribution Patterns on the Diagnosis of Synucleinopathies [abstract]. Mov Disord. 2025; 40 (suppl 1).
