ArticleThe journal of histochemistry and cytochemistry : official journal of the Histochemistry Society2020
Phosphorylated Alpha-Synuclein Within Cutaneous Autonomic Nerves of Patients With Parkinson's Disease: The Implications of Sample Thickness on Results.
Article in The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers, 2 of them syntheses that pooled it.
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The trial behind it
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Who cites it
40 citing papers in PubMed, 2 syntheses or guidelines pooled it, 48 citations in OpenAlex.
- Diagnostic biomarkers for α-synucleinopathies- state of the art and future developments: a systematic review.Molecular neurodegeneration · 2025Pooled it
- Skin α-synuclein assays in diagnosing Parkinson's disease: a systematic review and meta-analysis.Journal of neurology · 2025Pooled it
- Cutaneous alpha-synuclein deposition informs autonomic function in individuals with early-stage multiple system atrophy.Clinical autonomic research : official journal of the Clinical Autonomic Research Society · 2026Article
- Standardized protocol to detect phosphorylated α-synuclein in skin biopsies: recommendations from an expert panel.Molecular neurodegeneration · 2026Article
- Myelin damage in donor skin differentiates between synucleinopathies.NPJ Parkinson's disease · 2026Article
- Quantitative measures of total and phosphorylated alpha-synuclein in skin tissue as potential biomarkers for synucleinopathies.Journal of Parkinson's disease · 2026Article
- Cutaneous Phosphorylated Alpha-Synuclein in Lewy Body Dementia.Annals of clinical and translational neurology · 2026Article
- Peripheral immunochemical considerations in Parkinson disease: sources, targets and crosstalk mechanisms.Journal of translational medicine · 2026Review
- Skin Biopsy for Phosphorylated α-Synuclein in Mild Cognitive Impairment or Dementia Due to Lewy Body Disease in a Convenience Cohort from a Subspecialty Behavioral Neurology Practice.Movement disorders : official journal of the Movement Disorder Society · 2026Article
- A Novel 3D Semi-Automated Full Quantification Technique for Detection of Intraneural Phospho-α-Synuclein in Skin Biopsies.European journal of neurology · 2026Article
- Ten-Year Retrospective Study on the Diagnostic Value of Three-Site Skin Biopsy for Detecting pS129-α-Synuclein Biomarker: Cervical and Leg Dual-Site Biopsy as an Effective and Less Invasive Alternative.European journal of neurology · 2026Article
- Cutaneous α-Synuclein Pathology as a Differential Marker: A Histological and Statistical Comparison across Neurodegenerative Disease Groups.Journal of molecular neuroscience : MN · 2026Article
- Clinical utility of skin biopsy detection of phosphorylated alpha-synuclein in an outpatient practice.Frontiers in neurology · 2026Article
- The Role of Skin Innervation for Assessment of Neurological Involvement in Disorders: A Review.Brain sciences · 2025Review
- The Syn-D study: detection of cutaneous phosphorylated alpha-synuclein in mild cognitive impairment a trial protocol.Biomarkers in medicine · 2025Article
- Advancing Parkinson's diagnosis: seed amplification assay for α-synuclein detection in minimally invasive samples.Molecular and cellular biochemistry · 2025Review
- α-Synuclein in Parkinson's Disease: From Bench to Bedside.Medicinal research reviews · 2025Review
- Overlapping presence of β-amyloid, tau, p-tau, and α-synuclein in skin nerve fibers in Alzheimer's disease.Journal of neurology · 2025Article
- A pathophysiological biomarker combination separates Lewy body from non-Lewy body neurogenic orthostatic hypotension .Clinical autonomic research : official journal of the Clinical Autonomic Research Society · 2024Observational
- Evaluating the Diagnostic Potential of Combined Salivary and Skin Biomarkers in Parkinson's Disease.International journal of molecular sciences · 2024Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
The detection of cutaneous phosphorylated alpha-synuclein (P-syn) in patients with Parkinson's disease (PD) has ranged from 30% to 100% across different studies. We hypothesize that part of the variability in P-syn detection is due to methodological differences using sections of different tissue thickness. Three skin biopsies were obtained from 29 individuals with PD and 21 controls. Tissues were cut into 10-, 20-, and 50-µm-thick sections and double-stained with protein gene product (PGP) 9.5 and P-syn. We quantified the deposition of P-syn with and without PGP 9.5 in sweat glands, pilomotor muscle, and blood vessels using confocal digital images of autonomic structures. Overall, the P-syn-positive rates with PGP 9.5 colocalization in subjects with PD were 100% using 50 µm sections, 90% using 20 µm sections, and 73% using 10 µm sections with 100% specificity. (No P-syn was detected within control subjects.) Without PGP 9.5, colocalization of the P-syn-positive rates was 100% for all samples, but specificity dropped below 70%. In this study, double-immunostained 50 µm skin biopsy tissue sections are superior to 20 and 10 µm tissue sections at detecting P-syn in subjects with PD. The increased sensitivity is likely secondary to a combination of greater volume of tissue analyzed and improved visualization of nerve fiber architecture.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.