Frontiers in Neurology (May 2024)
Peripheral cutaneous synucleinopathy characteristics in genetic Parkinson’s disease
- Yanpeng Yuan,
- Yanpeng Yuan,
- Yanpeng Yuan,
- Yangyang Wang,
- Yangyang Wang,
- Yangyang Wang,
- Minglei Liu,
- Haiyang Luo,
- Haiyang Luo,
- Haiyang Luo,
- Haiyang Luo,
- Xiaojing Liu,
- Xiaojing Liu,
- Xiaojing Liu,
- Lanjun Li,
- Lanjun Li,
- Lanjun Li,
- Chengyuan Mao,
- Chengyuan Mao,
- Chengyuan Mao,
- Chengyuan Mao,
- Ting Yang,
- Ting Yang,
- Ting Yang,
- Shuo Li,
- Shuo Li,
- Shuo Li,
- Xiaoyun Zhang,
- Yuan Gao,
- Yuan Gao,
- Yuan Gao,
- Yuan Gao,
- Yuming Xu,
- Yuming Xu,
- Yuming Xu,
- Yuming Xu,
- Jing Yang,
- Jing Yang,
- Jing Yang,
- Jing Yang
Affiliations
- Yanpeng Yuan
- Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
- Yanpeng Yuan
- Henan Key Laboratory of Cerebrovascular Diseases, Zhengzhou University, Zhengzhou, Henan, China
- Yanpeng Yuan
- Institute of Neuroscience, Zhengzhou University, Zhengzhou, Henan, China
- Yangyang Wang
- Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
- Yangyang Wang
- Henan Key Laboratory of Cerebrovascular Diseases, Zhengzhou University, Zhengzhou, Henan, China
- Yangyang Wang
- Institute of Neuroscience, Zhengzhou University, Zhengzhou, Henan, China
- Minglei Liu
- Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
- Haiyang Luo
- Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
- Haiyang Luo
- Henan Key Laboratory of Cerebrovascular Diseases, Zhengzhou University, Zhengzhou, Henan, China
- Haiyang Luo
- Institute of Neuroscience, Zhengzhou University, Zhengzhou, Henan, China
- Haiyang Luo
- NHC Key Laboratory of Prevention and Treatment of Cerebrovascular Disease, Zhengzhou, Henan, China
- Xiaojing Liu
- Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
- Xiaojing Liu
- Henan Key Laboratory of Cerebrovascular Diseases, Zhengzhou University, Zhengzhou, Henan, China
- Xiaojing Liu
- Institute of Neuroscience, Zhengzhou University, Zhengzhou, Henan, China
- Lanjun Li
- Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
- Lanjun Li
- Henan Key Laboratory of Cerebrovascular Diseases, Zhengzhou University, Zhengzhou, Henan, China
- Lanjun Li
- Institute of Neuroscience, Zhengzhou University, Zhengzhou, Henan, China
- Chengyuan Mao
- Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
- Chengyuan Mao
- Henan Key Laboratory of Cerebrovascular Diseases, Zhengzhou University, Zhengzhou, Henan, China
- Chengyuan Mao
- Institute of Neuroscience, Zhengzhou University, Zhengzhou, Henan, China
- Chengyuan Mao
- NHC Key Laboratory of Prevention and Treatment of Cerebrovascular Disease, Zhengzhou, Henan, China
- Ting Yang
- Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
- Ting Yang
- Henan Key Laboratory of Cerebrovascular Diseases, Zhengzhou University, Zhengzhou, Henan, China
- Ting Yang
- Institute of Neuroscience, Zhengzhou University, Zhengzhou, Henan, China
- Shuo Li
- Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
- Shuo Li
- Henan Key Laboratory of Cerebrovascular Diseases, Zhengzhou University, Zhengzhou, Henan, China
- Shuo Li
- Institute of Neuroscience, Zhengzhou University, Zhengzhou, Henan, China
- Xiaoyun Zhang
- Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
- Yuan Gao
- Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
- Yuan Gao
- Henan Key Laboratory of Cerebrovascular Diseases, Zhengzhou University, Zhengzhou, Henan, China
- Yuan Gao
- Institute of Neuroscience, Zhengzhou University, Zhengzhou, Henan, China
- Yuan Gao
- NHC Key Laboratory of Prevention and Treatment of Cerebrovascular Disease, Zhengzhou, Henan, China
- Yuming Xu
- Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
- Yuming Xu
- Henan Key Laboratory of Cerebrovascular Diseases, Zhengzhou University, Zhengzhou, Henan, China
- Yuming Xu
- Institute of Neuroscience, Zhengzhou University, Zhengzhou, Henan, China
- Yuming Xu
- NHC Key Laboratory of Prevention and Treatment of Cerebrovascular Disease, Zhengzhou, Henan, China
- Jing Yang
- Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
- Jing Yang
- Henan Key Laboratory of Cerebrovascular Diseases, Zhengzhou University, Zhengzhou, Henan, China
- Jing Yang
- Institute of Neuroscience, Zhengzhou University, Zhengzhou, Henan, China
- Jing Yang
- NHC Key Laboratory of Prevention and Treatment of Cerebrovascular Disease, Zhengzhou, Henan, China
- DOI
- https://doi.org/10.3389/fneur.2024.1404492
- Journal volume & issue
-
Vol. 15
Abstract
BackgroundCutaneous 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.ObjectiveThis study aimed to detect p-α-syn deposition characteristic in rare genetic PD patients with CHCHD2 or RAB39B 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.MethodsWe performed four skin biopsy samples from the distal leg (DL) and proximal neck (C7) of 161 participants, including four patients with CHCHD2 mutations, two patients with RAB39B mutations, 16 patients with PRKN mutations, 14 patients with LRRK2 mutations, five patients with GBA 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.ResultsP-α-syn was deposited in the peripheral cutaneous nerves of PD patients with CHCHD2, LRRK2, or GBA mutations but not in those with RAB39B or PRKN 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 LRRK2 and GBA mutation patients revealed prion-like activity.ConclusionP-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.
Keywords
