Alpha-Synuclein in Skin Nerve Fibers as a Biomarker for Alpha-Synucleinopathies

The common pathological features of synucleinopathies are abnormal aggregates of the synaptic protein alpha-synuclein (αSN) in the cytoplasm of neurons or glia. These abnormal aggregates appear several years before the onset of clinical manifestations, and so the early detection of αSN in body fluids or peripheral tissues (e.g., cerebrospinal fluid, colonic mucosa, salivary glands, and skin) is considered a potential tool for identifying synucleinopathies. Performing a skin biopsy is a practical option because it is a relatively noninvasive, safe, and reliable method to measure αSN deposition in the peripheral nervous system. Moreover, there is growing research interest in the use of cutaneous synuclein deposition as a biomarker for synucleinopathies. The aim of this study was to interpret the current data on cutaneous αSN deposition and present the current perspectives and future prospects.