A Kuzkina1, L Schulmeyer2, C-M Monoranu2, J Volkmann2, C Sommer2, K Doppler2. 1. Department of Neurology, University Hospital Würzburg, Josef-Schneider-Str. 11, 97080, Würzburg, Germany. Electronic address: kuzkina_a@ukw.de. 2. Department of Neurology, University Hospital Würzburg, Josef-Schneider-Str. 11, 97080, Würzburg, Germany.
Abstract
INTRODUCTION: Phosphorylated α-synuclein (p-α-syn) can be detected in dermal nerve fibers of patients with Parkinson's disease (PD) and multiple system atrophy (MSA). Here we investigated whether p-α-syn in the cutaneous nerve fibers represents misfolded aggregated protein. METHODS: Using immunofluorescence with conformation specific antibodies and digestion with proteinase K (PK), we studied skin biopsies from a cohort of patients with early stage PD (Hoehn and Yahr I/II, n=27), MSA with predominant parkinsonism (MSA-P, n=8) and normal controls (n=21). RESULTS: We could show that α-synuclein (α-syn) found in the dermal nerve fibers in PD and MSA-P is not only phosphorylated but represents PK resistant and truncated aggregated protein. Comparison with a post mortem midbrain sample revealed a similar staining pattern of pathologic α-syn lesions in the PD brain. CONCLUSION: Immunostaining of nerve fibers with different conformation specific antibodies and digestion with PK gave comparable results between midbrain and skin sections, showing that cutaneous nerve deposits of α-syn are structurally similar to Lewy pathology in the brain and are highly specific for synucleinopathy.
INTRODUCTION: Phosphorylated α-synuclein (p-α-syn) can be detected in dermal nerve fibers of patients with Parkinson's disease (PD) and multiple system atrophy (MSA). Here we investigated whether p-α-syn in the cutaneous nerve fibers represents misfolded aggregated protein. METHODS: Using immunofluorescence with conformation specific antibodies and digestion with proteinase K (PK), we studied skin biopsies from a cohort of patients with early stage PD (Hoehn and Yahr I/II, n=27), MSA with predominant parkinsonism (MSA-P, n=8) and normal controls (n=21). RESULTS: We could show that α-synuclein (α-syn) found in the dermal nerve fibers in PD and MSA-P is not only phosphorylated but represents PK resistant and truncated aggregated protein. Comparison with a post mortem midbrain sample revealed a similar staining pattern of pathologic α-syn lesions in the PD brain. CONCLUSION: Immunostaining of nerve fibers with different conformation specific antibodies and digestion with PK gave comparable results between midbrain and skin sections, showing that cutaneous nerve deposits of α-syn are structurally similar to Lewy pathology in the brain and are highly specific for synucleinopathy.
Authors: Alain Ndayisaba; Ariana T Pitaro; Andrew S Willett; Kristie A Jones; Claudio Melo de Gusmao; Abby L Olsen; Jisoo Kim; Eero Rissanen; Jared K Woods; Sharan R Srinivasan; Anna Nagy; Amanda Nagy; Merlyne Mesidor; Steven Cicero; Viharkumar Patel; Derek H Oakley; Idil Tuncali; Katherine Taglieri-Noble; Emily C Clark; Jordan Paulson; Richard C Krolewski; Gary P Ho; Albert Y Hung; Anne-Marie Wills; Michael T Hayes; Jason P Macmore; Luigi Warren; Pamela G Bower; Carol B Langer; Lawrence R Kellerman; Christopher W Humphreys; Bonnie I Glanz; Elodi J Dielubanza; Matthew P Frosch; Roy L Freeman; Christopher H Gibbons; Nadia Stefanova; Tanuja Chitnis; Howard L Weiner; Clemens R Scherzer; Sonja W Scholz; Dana Vuzman; Laura M Cox; Gregor Wenning; Jeremy D Schmahmann; Peter Novak; Geoffrey S Young; Mel B Feany; Tarun Singhal; Vikram Khurana Journal: Cerebellum Date: 2022-10-03 Impact factor: 3.648
Authors: Zerui Wang; Katelyn Becker; Vincenzo Donadio; Sandra Siedlak; Jue Yuan; Masih Rezaee; Alex Incensi; Anastasia Kuzkina; Christina D Orrú; Curtis Tatsuoka; Rocco Liguori; Steven A Gunzler; Byron Caughey; Maria E Jimenez-Capdeville; Xiongwei Zhu; Kathrin Doppler; Li Cui; Shu G Chen; Jiyan Ma; Wen-Quan Zou Journal: JAMA Neurol Date: 2020-09-28 Impact factor: 18.302