Skin Biopsy as a Diagnostic Tool for Synucleinopathies

Abstract

Studies published in the last decade identified skin biopsies as a promising source of material for detecting alpha-synuclein (αSN). Alpha-synuclein gets deposited in the skin of patients with synucleinopathies, and therefore, a skin biopsy can be used to diagnose and confirm these diseases histopathologically. A skin biopsy can also be helpful for studies focusing on the nature of αSN deposits. The most important aspects of a biomarker are sensitivity, specificity, and technical feasibility. The potential for a skin biopsy to become the clinical tool of choice as a reliable biomarker for diagnosing synucleinopathies appears to be high, with consistently high sensitivity (>80%) and specificity approaching 100%. The review aims to provide an overview of the factors impacting skin biopsy's sensitivity, specificity, and feasibility in detecting dermal αSN deposits.

Keywords: alpha-synuclein; alpha-synucleinopathies; dementia with lewy bodies; multiple system atrophy; parkinson' s disease; skin biopsy.

Figure 1. Photomicrograph of a skin biopsy of Parkinson’s disease

The skin biopsy sections were cut 20-µm thick, fixed with 4% paraformaldehyde before cryopreserving, and stained with double immunofluorescence stains (anti-protein-gene-product 9.5, green, Zytomed Systems, 1:1000, and anti-p-αSN, red, Covance, 1:500). Intraaxonal p-αSN deposits are indicated with the arrows. Reprinted from Journal of Parkinson's Disease, vol. 11, Kathrin Doppler, Detection of Dermal Alpha-Synuclein Deposits as a Biomarker for Parkinson's Disease, pp. 937-947, Copyright 2021, with permission from IOS Press. The publication is available at IOS Press at http://dx.doi.org/10.3233/JPD-202489 [13] p-αSN: phosphorylated alpha-synuclein