MedElevator
Войти в исследования European journal of neurology · 2026
A Novel 3D Semi-Automated Full Quantification Technique for Detection of Intraneural Phospho-α-Synuclein in Skin Biopsies.
СтатьяНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Lonczewski Sophia, Bader Verian, Ortmann Louisa, Basner Louisa, Stücker Markus, Gold Ralf, Scherbaum Raphael, Kwon Eun Hae, Winklhofer Konstanze F, Tönges Lars
Аннотация
BACKGROUND: Parkinson'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.
METHODS: In 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.
RESULTS: Our 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.
CONCLUSIONS: This 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.
METHODS: In 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.
RESULTS: Our 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.
CONCLUSIONS: This 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.