Skin Biopsies Show Promise as Diagnostic Tool for Synucleinopathies Such as Parkinson Disease

High rates of phosphorylated α-synuclein can be detected through skin biopsies of individuals with synucleinopathies such as Parkinson disease, according to research published online in JAMA. 

Researchers are urgently seeking a reliable diagnostic biomarker for synucleinopathies such as Parkinson disease [PD], dementia with Lewy bodies [DLB], multiple system atrophy [MSA], and pure autonomic failure [PAF]. The detection of cutaneous phosphorylated α-synuclein through immunohistochemical testing may be a sensitive and specific clinical tool for diagnosing these disorders in patients.

Between February 2021 and March 2023, a blinded, 30-site, cross-sectional study was conducted on academic and community-based neurology practices. The study included patients aged 40 to 99 with synucleinopathies, as well as control participants without symptoms of neurodegenerative disease. Detailed neurological examinations and skin biopsies were performed to detect phosphorylated α-synuclein, with final participant diagnoses determined by an expert review panel blinded to pathologic data. The main outcomes of the study focused on the detection rates of cutaneous α-synuclein in patients with synucleinopathies and control participants.

Of the 428 participants involved, 343 were included in the main analysis, with an average age of 69.5 years and more than half were male. After careful evaluation by experts, 223 were diagnosed with a synucleinopathy and 120 were classified as controls. The presence of cutaneous phosphorylated α-synuclein in skin biopsies was found to be high in individuals with PD, MSA, DLB, and PAF, while only a small percentage of controls tested positive for this marker.

“In this cross-sectional study, a high proportion of individuals meeting clinical consensus criteria for PD, DLB, MSA, and PAF had phosphorylated α-synuclein detected by skin biopsy,” said researchers. “Further research is needed in unselected clinical populations to externally validate the findings and fully characterize the potential role of skin biopsy detection of phosphorylated α-synuclein in clinical care.” 

Reference
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