Peripheral cutaneous synucleinopathy characteristics in genetic Parkinson's disease

• Published in: Frontiers in neurology Vol. 15; p. 1404492
• Main Authors: Yuan, Yanpeng, Wang, Yangyang, Liu, Minglei, Luo, Haiyang, Liu, Xiaojing, Li, Lanjun, Mao, Chengyuan, Yang, Ting, Li, Shuo, Zhang, Xiaoyun, Gao, Yuan, Xu, Yuming, Yang, Jing
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 01.05.2024
• Subjects: CHCHD2; genetic Parkinson’s disease; Neurology; RAB39B; SAA; skin biopsy; α-synuclein; RAB39B; CHCHD2; SAA; genetic Parkinson’s disease; skin biopsy; α-synuclein
• ISSN: 1664-2295; 1664-2295
• DOI: 10.3389/fneur.2024.1404492

Cutaneous phosphorylated alpha-synuclein (p-α-syn) deposition is an important biomarker of idiopathic Parkinson's disease (iPD). Recent studies have reported synucleinopathies in patients with common genetic forms of PD. This study aimed to detect p-α-syn deposition characteristic in rare genetic PD patients with or mutations. Moreover, this study also aimed to describe peripheral alpha-synuclein prion-like activity in genetic PD patients, and acquire whether the cutaneous synucleinopathy characteristics of genetic PD are consistent with central neuropathologies. We performed four skin biopsy samples from the distal leg (DL) and proximal neck (C7) of 161 participants, including four patients with mutations, two patients with mutations, 16 patients with mutations, 14 patients with mutations, five patients with mutations, 100 iPD patients, and 20 healthy controls. We detected cutaneous synucleinopathies using immunofluorescence staining and a seeding amplification assay (SAA). A systematic literature review was also conducted, involving 64 skin biopsies and 205 autopsies of genetic PD patients with synucleinopathy. P-α-syn was deposited in the peripheral cutaneous nerves of PD patients with , , or mutations but not in those with or mutations. There were no significant differences in the location or rate of α-syn-positive deposits between genetic PD and iPD patients. Peripheral cutaneous synucleinopathy appears to well represent brain synucleinopathy of genetic PD, especially autosomal dominant PD (AD-PD). Cutaneous α-synuclein SAA analysis of iPD and and mutation patients revealed prion-like activity. P-α-syn deposition in peripheral cutaneous nerves, detected using SAA and immunofluorescence staining, may serve as an accurate biomarker for genetic PD and iPD in the future.