ArticleActa neuropathologica2014
Cutaneous neuropathy in Parkinson's disease: a window into brain pathology.
Article in Acta neuropathologica, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 118 papers, 3 of them syntheses that pooled it.
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Who cites it
118 citing papers in PubMed, 3 syntheses or guidelines pooled it, 230 citations in OpenAlex.
- Skin α-synuclein assays in diagnosing Parkinson's disease: a systematic review and meta-analysis.Journal of neurology · 2025Pooled it
- Wearable Health Technology to Quantify the Functional Impact of Peripheral Neuropathy on Mobility in Parkinson's Disease: A Systematic Review.Sensors (Basel, Switzerland) · 2020Pooled it
- An analysis of genetically regulated gene expression across multiple tissues implicates novel gene candidates in Alzheimer's disease.Alzheimer's research & therapy · 2020Pooled it
- Characterizing Cutaneous α-Synuclein Deposition and Seeding Activity in Parkinson's Disease Subtypes.Annals of clinical and translational neurology · 2026Article
- Standardized protocol to detect phosphorylated α-synuclein in skin biopsies: recommendations from an expert panel.Molecular neurodegeneration · 2026Article
- Quantitative measures of total and phosphorylated alpha-synuclein in skin tissue as potential biomarkers for synucleinopathies.Journal of Parkinson's disease · 2026Article
- Article
- Approach to Low Body Temperature or Mild Hypothermia in the Geriatric Population: A Narrative Review.Journal of clinical medicine research · 2026Review
- Cutaneous α-Synuclein Pathology as a Differential Marker: A Histological and Statistical Comparison across Neurodegenerative Disease Groups.Journal of molecular neuroscience : MN · 2026Article
- Neuroimaging and Pathology Biomarkers in Parkinson's Disease and Parkinsonism.Brain sciences · 2026Article
- Prevalence and Characteristics of Itch in Patients with Parkinson's Disease.Acta dermato-venereologica · 2025Article
- Cutaneous nerve fiber pathology and function in Parkinson's disease and atypical parkinsonism - a cohort study.NPJ Parkinson's disease · 2025Article
- Alpha-Synuclein Seed Amplification Assays in Parkinson's Disease: A Systematic Review and Network Meta-Analysis.Clinics and practice · 2025Review
- α-Synuclein in Parkinson's Disease: From Bench to Bedside.Medicinal research reviews · 2025Review
- Neuronal threshold functions: Determining symptom onset in neurological disorders.Progress in neurobiology · 2024Review
- Large-fiber neuropathy in Parkinson's disease: a narrative review.Neurological research and practice · 2024Review
- Review
- Hearing dysfunction heralds an increase in non-motor burden and a worse quality of life in Parkinson's disease: new insights from non-motor spectrum.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2024Article
- Tau seeding activity in skin biopsy differentiates tauopathies from synucleinopathies.NPJ Parkinson's disease · 2024Article
- Skin nerve phosphorylated α-synuclein in the elderly.Journal of neuropathology and experimental neurology · 2024Article
58 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The deposition of alpha-synuclein in the brain, the neuropathological hallmark of Parkinson's disease (PD), follows a distinct anatomical and temporal sequence. This study aimed to characterize alpha-synuclein deposition in cutaneous nerves from patients with PD. We further strived to explore whether peripheral nerve involvement is intrinsic to PD and reflective of known features of brain pathology, which could render it a useful tool for pathogenetic studies and pre-mortem histological diagnosis of PD. We obtained skin biopsies from the distal and proximal leg, back and finger of 31 PD patients and 35 controls and quantified the colocalization of phosphorylated alpha-synuclein in somatosensory and autonomic nerve fibers and the pattern of loss of different subtypes of dermal fibers. Deposits of phosphorylated alpha-synuclein were identified in 16/31 PD patients but in 0/35 controls (p < 0.0001). Quantification of nerve fibers revealed two types of peripheral neurodegeneration in PD: (1) a length-dependent reduction of intraepidermal small nerve fibers (p < 0.05) and (2) a severe non-length-dependent reduction of substance P-immunoreactive intraepidermal nerve fibers (p < 0.0001). The latter coincided with a more pronounced proximal manifestation of alpha-synuclein pathology in the skin. The histological changes did not correlate with markers of levodopa toxicity such as vitamin B12 deficiency. Our findings suggest that loss of peripheral nerve fibers is an intrinsic feature of PD and that peripheral nerve changes may reflect the two types of central alpha-synuclein-related PD pathology, namely neuronal death and axonal degeneration. Detection of phosphorylated alpha-synuclein in dermal nerve fibers might be a useful diagnostic test for PD with high specificity but low sensitivity.
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