Can Skin Biopsy Test for Parkinson Disease Detect α-Synuclein Deposition?

A high percentage of patients with Parkinson disease (PD), dementia with Lewy bodies (DLB), multiple system atrophy (MSA), and pure autonomic failure (PAF) have positivity for phosphorylated α-synuclein (P-SYN), as detected by skin biopsy, according to study results published in JAMA.

Due to the unmet need for a reliable diagnostic biomarker, researchers of a multicenter cross-sectional study aimed to determine the positivity rate of P-SYN deposition via skin biopsy in patients with PD, DLB, MSA, and PAF.

Eligible participants were aged between 40 and 99 and had a clinical diagnosis of PD, DLB, MSA, or PAF. Control participants were age-matched and did not have a history of synucleinopathy. All participants underwent evaluation by the Movement Disorders Society Unified Parkinson Disease Rating Scale (MDS-UPDRS) and Montreal Cognitive Assessment, and completed questionnaires on disease activity and quality of life. Participants also underwent a skin biopsy.

Primary study outcome was rates of detection of P-SYN deposits by skin biopsy in patients with PD, DLB, MSA, PAF, and control participants without synucleinopathy.

Between 2021 and 2023, 428 participants were enrolled in the study, of whom 277 were patients with synucleinopathy and 151 were comparators.

A total of 343 participants (mean age, 69.5; 51.0% men) were included in the primary analysis. Of these, 223 met the criteria for synucleinopathy, with the majority having PD (28.0%). Overall, 95.5% of patients with a diagnosis of synucleinopathy had cutaneous P-SYN, as detected by skin biopsy; 92.7% had PD, 98.2% had MSA, 96% DLB, and 100% had PAF.

Participants with undifferentiated synucleinopathy and those with an unknown diagnosis were excluded from the secondary analysis. Results showed lack of an association between time since diagnosis and P-SYN positivity, as well as a link between P-SYN deposits in the subepidermal plexus and different synucleinopathy subtypes.

Total P-SYN scores correlated with scores measured by MDS-UPDRS and Montreal Cognitive Assessment (both P <.001), as well as the disease-specific and quality of life questionnaires, including the 39-item Parkinson Disease Questionnaire and European Quality of Life (P <.001 for both).

Overall, 1284 biopsies were conducted among 428 participants. No infections or serious complications were noted.

Limitations of the analysis included the lack of confirmation of the diagnoses; sensitivity of detection for early stages of the disease was not accounted; and disease mimics, such as tremor and palsy, were not adjusted for among control participants.

“Further research is needed in unselected clinical populations to externally validate the findings and fully characterize the potential role of skin biopsy detection of P-SYN in clinical care,” the researchers concluded.

Disclosure: Multiple study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of the authors’ disclosures.