Tau seeding activity in skin biopsy differentiates tauopathies from synucleinopathies
Dellarole, Ilaria Linda (Fondazione IRCCS Istituto Neurologico Carlo Besta (Milà, Itàlia))
Vacchi, Elena (Università della Svizzera Italiana)
Ruiz Barrio, Iñigo (Institut de Recerca Sant Pau)
Pinton, Sandra (Ente Ospedaliero Cantonale)
Raimondi, Andrea (Università della Svizzera italiana)
Rossi, Stefania (Ente Ospedaliero Cantonale)
Morandi, Sara (Ente Ospedaliero Cantonale)
Bianco, Giovanni (Ente Ospedaliero Cantonale)
Begum Bacinoglu, Merve (Fondazione IRCCS Istituto Neurologico Carlo Besta (Milà, Itàlia))
Lombardo, Annalisa (Fondazione IRCCS Istituto Neurologico Carlo Besta (Milà, Itàlia))
Celauro, Luigi (Scuola Internazionale Superiore Di Studi Avanzati (SISSA))
Staedler, Claudio (Ente Ospedaliero Cantonale)
Galati, Salvatore (Ente Ospedaliero Cantonale)
Pagonabarraga Mora, Javier (Institut de Recerca Sant Pau)
Kulisevsky, Jaime (Institut de Recerca Sant Pau)
Legname, Giuseppe (Scuola Internazionale Superiore Di Studi Avanzati (SISSA))
Gobbi, Claudio (University Hospital Basel (Basilea, Suïssa))
Kaelin-Lang, Alain (University of Bern)
Moda, Fabio (Fondazione IRCCS Istituto Neurologico Carlo Besta (Milà, Itàlia))
Melli, Giorgia (Ente Ospedaliero Cantonale)
Universitat Autònoma de Barcelona

Fecha:	2024
Resumen:	Most neurodegenerative diseases lack definitive diagnostic tests, and the identification of easily accessible and reliable biomarkers remains a critical unmet need. Since tau protein is highly expressed in skin of tauopathies patients, we aimed to exploit the ultrasensitive seeding activity assay (SAA) to assess tau seeding activity in skin of patients with tauopathies. In this multicentric, case-control study, patients with tauopathies and synucleinopathies were consecutively recruited and sex-matched to healthy controls (HC). Subjects underwent a double 3 mm skin biopsy in cervical area and ankle. Skin tau-SAA, using TauK18 and TauK19 as reaction substrates for 4R and 3R isoforms, seeding score, clinical scales, biochemical and morphological characterization of SAA end-products were evaluated. We analyzed 58 subjects: 24 tauopathies (18 progressive supranuclear palsy, PSP, and 6 corticobasal degeneration, CBD), 20 synucleinopathies (14 Parkinson's disease, PD, and 6 multiple system atrophy, MSA), and 14 HC. PSP and CBD showed higher tau seeding activity at both anatomical sites. A greater sensitivity of 4R-SAA than 3R-SAA was observed. 4R tau-SAA identified tauopathies with 71% sensitivity and 93% specificity. Accuracy was higher for PSP than CBD: PSP vs HC / PD (AUC 0. 825), while CBD vs HC / PD (AUC 0. 797), and PSP vs MSA (AU 0. 778). SAA end-products showed differences in biochemical and morphological characterization according to the anatomical site. Skin tau-SAA identifies tauopathies with good accuracy and can be used to implement the in-vivo clinical diagnosis of patients with neurodegenerative diseases. Further characterization of peripheral tau seed in skin may elucidate the structure of tau deposits in brain.
Derechos:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Lengua:	Anglès
Documento:	Article ; recerca ; Versió publicada
Publicado en:	NPJ Parkinson's disease, Vol. 10 Núm. 1 (december 2024) , p. 116, ISSN 2373-8057

DOI: 10.1038/s41531-024-00728-9
PMID: 38879633

12 p, 3.3 MB

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Documentos de investigación > Documentos de los grupos de investigación de la UAB > Centros y grupos de investigación (producción científica) > Ciencias de la salud y biociencias > Institut de Recerca Sant Pau
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