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The aggregation state of α-synuclein deposits in dermal nerve fibers of patients with Parkinson's disease resembles that in the brain.
Parkinsonism & related Disorders 2019 July
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.
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.
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