Evidence map›Paper›PMID 39805051›Full record

Observational studyNeurology2025

Pathophysiological Significance of α-Synuclein in Sympathetic Nerves: In Vivo Observations.

Risa Isonaka, Patti Sullivan, David S Goldstein

Abstract readObservational Study
In one paragraph

Observational study in Neurology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed.

  1. Preclinical Catecholaminergic Biomarkers of Central Lewy Body Diseases.Journal of clinical neurology (Seoul, Korea) · 2026
    Review
  2. Article
  3. Redefining Non-Motor Symptoms in Parkinson's Disease.Journal of personalized medicine · 2025
    Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

3 authors.

Risa IsonakaFrom the Autonomic Medicine Section, Clinical Neurosciences Program, Division of Intramural Research, National Institute of Neurological Disorders and Stroke, NIH, Bethesda, MD.ORCID 0000-0002-7289-8257
Patti SullivanFrom the Autonomic Medicine Section, Clinical Neurosciences Program, Division of Intramural Research, National Institute of Neurological Disorders and Stroke, NIH, Bethesda, MD.ORCID 0009-0000-8627-8270
David S GoldsteinFrom the Autonomic Medicine Section, Clinical Neurosciences Program, Division of Intramural Research, National Institute of Neurological Disorders and Stroke, NIH, Bethesda, MD.ORCID 0000-0002-5709-9940

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

BACKGROUND AND

objectivesLewy body diseases (LBDs) such as Parkinson disease (PD) feature increased deposition of α-synuclein (α-syn) in cutaneous sympathetic noradrenergic nerves. The pathophysiologic significance of sympathetic intraneuronal α-syn is unclear. We reviewed data about immunoreactive α-syn, tyrosine hydroxylase (TH, a marker of catecholaminergic fibers), and the sympathetic neurotransmitter norepinephrine (NE) in skin biopsies from control participants and patients with PD, the related LBD pure autonomic failure (PAF), the non-LBD synucleinopathy multiple system atrophy (MSA), or neurologic postacute sequelae of severe acute respiratory syndrome coronavirus 2 (neuro-PASC).

methodsIn a retrospective observational study, we reviewed data about α-syn-TH colocalization indexes and immunoreactive α-syn and TH signal intensities in arrector pili muscles, blood vessels, and sweat glands from neck skin biopsies and NE concentrations in simultaneously obtained thigh skin biopsies from participants studied at the NIH Clinical Center. LBD, MSA, and control group data were assessed by analyses of variance with the Tukey post hoc test for multiple comparisons. Similar analyses were performed for patients with PD or neuro-PASC vs control.

resultsDermal α-syn-TH colocalization indexes and α-syn signal intensities from neck skin biopsies were examined in 18 controls (mean age 58 years, 50% female) and 53 LBD (66, 34%), 15 MSA (61, 33%), and 11 neuro-PASC (52, 82%) patients. The LBD group had higher α-syn-TH colocalization indexes than the controls (mean difference = 1.495, 95% CI 1.081-1.909, DISCUSSION: LBDs and neuro-PASC entail increased α-syn-TH colocalization indexes in skin biopsies, without evidence of local denervation or noradrenergic deficiency. The results fail to support toxicity of intraneuronal α-syn in cutaneous sympathetic noradrenergic nerves in either LBDs or neuro-PASC. The neuro-PASC data raise the possibility of sympathetic intraneuronal α-syn deposition as part of postinfectious immune or inflammatory processes.

Indexed as

alpha-SynucleinLewy Body DiseaseParkinson DiseaseSkinSympathetic Nervous SystemAgedCOVID-19FemaleHumansMaleMiddle AgedMultiple System AtrophyNorepinephrinePure Autonomic FailureRetrospective StudiesSweat Glandsalpha-SynucleinNorepinephrineTyrosine 3-Monooxygenase

Identifiers

PMID39805051
PMCPMC11735147

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.