{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,6]],"date-time":"2026-05-06T08:19:06Z","timestamp":1778055546992,"version":"3.51.4"},"reference-count":42,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T00:00:00Z","timestamp":1776384000000},"content-version":"vor","delay-in-days":16,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T00:00:00Z","timestamp":1775001600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Euro J of Neurology"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Parkinson's disease (PD) and multiple system atrophy (MSA) are synucleinopathies marked by \u03b1\u2010synuclein aggregation, while progressive supranuclear palsy (PSP) is a tauopathy. Clinical overlap between these diseases complicates diagnosis. Detection of intraneural S129 phospho\u2010\u03b1\u2010synuclein (p\u03b1Syn) 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 p\u03b1Syn burden\u2014particularly relevant for this aim.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In this cross\u2010sectional study, we analyzed skin biopsies from 29 PD, 5 MSA, and 4 PSP patients. Samples obtained at C7 and Th12 were double\u2010immunostained with p\u03b1Syn and PGP9.5, a pan\u2010axonal neurite marker.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Our novel method digitizes biopsy sections semi\u2010automatically and performs computer\u2010assisted 3D signal reconstruction. The resulting full volumetric quantification of intraneural p\u03b1Syn load enables burden\u2010dependent test results based on ROC\u2010derived cut\u2010offs. 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 p\u03b1Syn load was significantly higher in PD and MSA compared to PSP (C7\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.004; Th12\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.002), with no difference between PD and MSA.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This novel technique refines IF by increasing objectivity and allowing gradual p\u03b1Syn\u2010burden assessment, offering potential as a confirmatory differential biomarker. Validation in larger, neuropathologically confirmed cohorts of these preliminary small\u2010group results is warranted to fully evaluate the diagnostic and prognostic potential.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/ene.70525","type":"journal-article","created":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T14:03:36Z","timestamp":1776434616000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A Novel\n                    <scp>3D<\/scp>\n                    Semi\u2010Automated Full Quantification Technique for Detection of Intraneural Phospho\u2010\u03b1\u2010Synuclein in Skin Biopsies"],"prefix":"10.1111","volume":"33","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-4106-2736","authenticated-orcid":false,"given":"Sophia","family":"Lonczewski","sequence":"first","affiliation":[{"name":"Department of Molecular Cell Biology, Institute of Biochemistry and Pathobiochemistry Ruhr University  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Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5564-5285","authenticated-orcid":false,"given":"Markus","family":"St\u00fccker","sequence":"additional","affiliation":[{"name":"Department of Dermatology and Allergology, St. Josef\u2010Hospital Ruhr University  Bochum Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7223-3052","authenticated-orcid":false,"given":"Ralf","family":"Gold","sequence":"additional","affiliation":[{"name":"Department of Neurology, St. Josef\u2010Hospital Ruhr University  Bochum Germany"},{"name":"Neurodegeneration Research, Centre for Protein Diagnostics (ProDi) Ruhr University  Bochum Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0700-4197","authenticated-orcid":false,"given":"Raphael","family":"Scherbaum","sequence":"additional","affiliation":[{"name":"Department of Neurology, St. 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