Evidence map›Paper›PMID 41995607›Full record

ArticleEuropean journal of neurology2026

A Novel 3D Semi-Automated Full Quantification Technique for Detection of Intraneural Phospho-α-Synuclein in Skin Biopsies.

Sophia Lonczewski, Verian Bader, Louisa Ortmann, Louisa Basner, Markus Stücker, Ralf Gold, Raphael Scherbaum, Eun Hae Kwon, Konstanze F Winklhofer, Lars Tönges

Abstract read
In one paragraph

Article in European journal of neurology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing 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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

10 authors.

Sophia LonczewskiDepartment of Molecular Cell Biology, Institute of Biochemistry and Pathobiochemistry, Ruhr University, Bochum, Germany.ORCID 0009-0006-4106-2736
Verian BaderDepartment of Molecular Cell Biology, Institute of Biochemistry and Pathobiochemistry, Ruhr University, Bochum, Germany.ORCID 0000-0001-5260-4728
Louisa OrtmannDepartment of Neurology, St. Josef-Hospital, Ruhr University, Bochum, Germany.ORCID 0009-0007-8641-4851
Louisa BasnerDepartment of Neurology, St. Josef-Hospital, Ruhr University, Bochum, Germany.ORCID 0009-0006-2778-5081
Markus StückerDepartment of Dermatology and Allergology, St. Josef-Hospital, Ruhr University, Bochum, Germany.ORCID 0000-0001-5564-5285
Ralf GoldDepartment of Neurology, St. Josef-Hospital, Ruhr University, Bochum, Germany.ORCID 0000-0002-7223-3052
Raphael ScherbaumDepartment of Neurology, St. Josef-Hospital, Ruhr University, Bochum, Germany.ORCID 0000-0003-0700-4197
Eun Hae KwonDepartment of Neurology, St. Josef-Hospital, Ruhr University, Bochum, Germany.ORCID 0009-0005-5051-0652
Konstanze F WinklhoferDepartment of Molecular Cell Biology, Institute of Biochemistry and Pathobiochemistry, Ruhr University, Bochum, Germany.ORCID 0000-0002-7256-8231
Lars TöngesDepartment of Neurology, St. Josef-Hospital, Ruhr University, Bochum, Germany.ORCID 0000-0001-6621-144X

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundParkinson's disease (PD) and multiple system atrophy (MSA) are synucleinopathies marked by α-synuclein aggregation, while progressive supranuclear palsy (PSP) is a tauopathy. Clinical overlap between these diseases complicates diagnosis. Detection of intraneural S129 phospho-α-synuclein (pαSyn) via immunofluorescence staining (IF) in skin biopsies shows diagnostic promise. However, prior studies rarely addressed differentiation between synucleinopathies and tauopathies and lacked assessment of varying pαSyn burden-particularly relevant for this aim.

methodsIn this cross-sectional study, we analyzed skin biopsies from 29 PD, 5 MSA, and 4 PSP patients. Samples obtained at C7 and Th12 were double-immunostained with pαSyn and PGP9.5, a pan-axonal neurite marker.

resultsOur novel method digitizes biopsy sections semi-automatically and performs computer-assisted 3D signal reconstruction. The resulting full volumetric quantification of intraneural pαSyn load enables burden-dependent test results based on ROC-derived cut-offs. Applied as a differential diagnostic test, it showed excellent discrimination of synucleinopathies from tauopathies, achieving AUCs of 0.912 (C7) and 0.934 (Th12), with 88.2% sensitivity and 100% specificity. Intraneural pαSyn load was significantly higher in PD and MSA compared to PSP (C7 p = 0.004; Th12 p = 0.002), with no difference between PD and MSA.

conclusionsThis novel technique refines IF by increasing objectivity and allowing gradual pαSyn-burden assessment, offering potential as a confirmatory differential biomarker. Validation in larger, neuropathologically confirmed cohorts of these preliminary small-group results is warranted to fully evaluate the diagnostic and prognostic potential.

Indexed as

alpha-SynucleinImaging, Three-DimensionalMultiple System AtrophyParkinson DiseaseSkinSupranuclear Palsy, ProgressiveAgedAged, 80 and overBiopsyCross-Sectional StudiesFemaleHumansMaleMiddle AgedPhosphorylationalpha-Synucleinmultiple system atrophyParkinson's diseaseprogressive supranuclear palsyskin biomarkerssynuclein

Identifiers

PMID41995607
PMCPMC13088975

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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.