Skin nerve phosphorylated a-synuclein deposits in idiopathic REM sleep behavior disorder

Objective: To test if phosphorylated a-synuclein (p-a-syn) deposits can be detected by means of skin biopsy in patients with idiopathic REM sleep behavior disorder (iRBD) as a potential early histopathologic marker of impending synucleinopathy. Methods: Proximal (cervical) and distal (legs) samples of skin biopsy were obtained from 12 patients with polysomnographically confirmed iRBD and 55 sex- and age-matched healthy controls (HC). P-a-syn deposits were assessed with a monoclonal antibody against p-a-syn at serine 129, disclosed by an immunofluorescence method. In addition, patients underwent an extensive workup in order to search for nonmotor symptoms and neuroimaging findings usually associated with impending neurodegeneration and to exclude subtle motor or cognitive signs. Results: P-a-syn deposits were detected in 9 (75%) out of 12 patients with iRBD and none of the HC. In iRBD, the sensitivity of the test was higher at the cervical site (67%) when compared to the leg site (58%). Conclusions: Our preliminary findings suggest that skin biopsy in patients with iRBD might be a safe and sensitive procedure to be further tested in order to detect p-a-syn deposits in the premotor stage of synucleinopathies. Classification of evidence: This study provides Class III evidence that p-a-syn skin deposits identify patients with iRBD.