A recent analysis published in Parkinsonism and Related Disorders examined how phosphorylated alpha-synuclein (P-SYN) skin biopsy results influenced real-world clinical decision-making at the Cleveland Clinic, a tertiary movement disorder center of excellence.¹ P-SYN skin biopsy assesses cutaneous aggregation of phosphorylated alpha-synuclein, a promising biomarker to support the differential diagnosis of patients with symptoms of synucleinopathies.

This real-world, retrospective observational cohort study evaluated all patients referred for a P‑SYN skin biopsy procedure between January and December 2024. Electronic medical record data were reviewed for 110 referred patients, approximately two thirds of whom (66.4%) completed the referral process (N=73/110, 66.4%). 73 participants underwent a comprehensive clinical evaluation prior to the P‑SYN skin biopsy procedure. Clinicians documented their diagnostic impressions and management plans both before and after receiving biopsy results, enabling assessment of the test’s impact on clinical decision‑making.

In a retrospective cohort of 73 patients, biopsy findings influenced patient management in 71.2% of cases (52/73), including reported changes to treatment and clinical recommendations. Biopsy findings also had a diagnostic impact in 65.8% of patients (48/73), including changes to a prior working diagnosis or clarification of an indeterminate diagnosis.

The authors noted several key study limitations.  The study was retrospective and observational, meaning that some bias is possible in the results. The study also has a modest sample size, affecting the rigor of the analysis and conclusions.

The findings from this publication are consistent with other published studies evaluating the use of cutaneous P-SYN biopsy findings in patients undergoing evaluation for suspected synucleinopathies. In one retrospective study conducted at a tertiary care center, clinicians reviewing medical records reported that use of P-SYN skin biopsy findings was associated with changes in diagnosis and treatment approach in 78% (N=76/97) of patients being evaluated for neurodegenerative disease.² In another retrospective study of patients with a suspected synucleinopathy, clinicians reported that P-SYN biopsy findings contributed to diagnostic and clinical management decisions in patients with suspected parkinsonism or dementia with Lewy bodies.³

See the publication

References

¹Anis S, Kundrick A, Callegari Piccinin C, 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
²J.R. Isaacson, R. Freeman, C.H. Gibbons, Clinical utility of synuclein skin biopsy in the diagnosis and evaluation of synucleinopathies, Front. Neurol. 15 (2024) 1510796.
³C.E. Gummerson, S. Tinaz, V. Santini, A. Zubair, Utilization of skin punch biopsy for the diagnosis of α-Synucleinopathy in clinical practice, Mov. Disord. Clin. Pract. 13 (1) (2026 Jan) 191–197.