Phosphorylated α-Synuclein Detectable by Skin Biopsy in Those with Synucleionopathies Including Parkinson Disease
According to study results published in JAMA, a high proportion of people with Parkinson disease (PD), multiple system atrophy (MSA), dementia with Lewy bodies (DLB), and pure autonomic failure (PAF) showed skin biopsies positive for cutaneous phosphorylated α-synuclein. The results suggest that skin biopsies, specifically those obtained using punch tools, may have potential future applications in the diagnosis of synucleionpathies as well as in clinical trial participant enrollment.
The blinded, cross-sectional study included data from 343 of 428 enrolled participants recruited from 30 US academic and community-based neurology practices from February 2021 to March 2023. Participants had a clinical diagnosis of PD (n=53), MSA (n=55), DLB (n=50), or PAF (n=22), evaluated using clinical consensus criteria and confirmed by an expert review panel. A control group included 120 participants with no history of synucleionopathy. Researchers obtained cutaneous skin samples from participants using a punch biopsy tool. Immunohistochemical assays were used to detect phosphorylated α-synuclein in the samples.
Cutaneous phosphorylated α-synuclein was detected in the skin biopsies of:
- 92.7% of participants with PD
- 98.2% of participants with MSA
- 96.0% of participants with DLB
- 100% of participants with PAF
- 3.3% of participants in the control group
“The sensitivity and specificity of the procedure are both high (more than 90 percent), which is very encouraging," stated Oskar Hansson, MD, PhD, professor of neurology at Lund University. “The method might, therefore, potentially be used to improve the diagnostic work-up in clinical practice but also when selecting appropriate patients for trials targeting α-synuclein.”
The study authors acknowledge that further research is necessary to validate findings and investigate any potential clinical applications of skin biopsies for the detection of synucleionopathy.