Titre :

Tau Monoclonal Antibody Generation Based on Humanized Yeast Models: IMPACT ON TAU OLIGOMERIZATION AND DIAGNOSTICS

Auteur(s) :

Rosseels, Joëlle [Auteur]
Catholic University of Leuven = Katholieke Universiteit Leuven [KU Leuven]
Van den Brande, Jeff [Auteur]
Catholic University of Leuven = Katholieke Universiteit Leuven [KU Leuven]
Violet, Marie-Luce [Auteur]
Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U837 [JPArc]
Jacobs, Dirk [Auteur]
Grognet, Pierre [Auteur]
Lopez, Juan [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 [UGSF]
Huvent, Isabelle [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 [UGSF]
Caldara, Marina [Auteur]
Catholic University of Leuven = Katholieke Universiteit Leuven [KU Leuven]
Swinnen, Erwin [Auteur]
Catholic University of Leuven = Katholieke Universiteit Leuven [KU Leuven]
Papegaey, Anthony [Auteur]
Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U837 [JPArc]
Caillierez, Raphaelle [Auteur]
Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U837 [JPArc]
Buée-Scherrer, Valerie [Auteur]
Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U837 [JPArc]
Engelborghs, Sebastiaan [Auteur]
University of Antwerp [UA]
Lippens, Guy [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 [UGSF]
Colin, Morvane [Auteur]
Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U837 [JPArc]
Buee, Luc [Auteur]
Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U837 [JPArc]
Galas, Marie-Christine [Auteur]
Lille Neurosciences & Cognition (LilNCog) - U 1172
Vanmechelen, Eugeen [Auteur]
Winderickx, Joris [Auteur]
Catholic University of Leuven = Katholieke Universiteit Leuven [KU Leuven]

Titre de la revue :

THE JOURNAL OF BIOLOGICAL CHEMISTRY

Numéro :

290

Pagination :

4059-4074

Date de publication :

2015-02-13

ISSN :

0021-9258

Mot(s)-clé(s) en anglais :

Disease
Antibody
Protein Folding
Tau Protein (Tau)
Yeast
Protein Oligomer

Discipline(s) HAL :

Chimie/Chimie théorique et/ou physique

Résumé en anglais : [en]

A link between Tau phosphorylation and aggregation has been shown in different models for Alzheimer disease, including yeast. We used human Tau purified from yeast models to generate new monoclonal antibodies, of which ...
Lire la suite >A link between Tau phosphorylation and aggregation has been shown in different models for Alzheimer disease, including yeast. We used human Tau purified from yeast models to generate new monoclonal antibodies, of which three were further characterized. The first antibody, ADx201, binds the Tau proline-rich region independently of the phosphorylation status, whereas the second, ADx215, detects an epitope formed by the Tau N terminus when Tau is not phosphorylated at Tyr18. For the third antibody, ADx210, the binding site could not be determined because its epitope is probably conformational. All three antibodies stained tangle-like structures in different brain sections of THY-Tau22 transgenic mice and Alzheimer patients, and ADx201 and ADx210 also detected neuritic plaques in the cortex of the patient brains. In hippocampal homogenates from THY-Tau22 mice and cortex homogenates obtained from Alzheimer patients, ADx215 consistently stained specific low order Tau oligomers in diseased brain, which in size correspond to Tau dimers. ADx201 and ADx210 additionally reacted to higher order Tau oligomers and presumed prefibrillar structures in the patient samples. Our data further suggest that formation of the low order Tau oligomers marks an early disease stage that is initiated by Tau phosphorylation at N-terminal sites. Formation of higher order oligomers appears to require additional phosphorylation in the C terminus of Tau. When used to assess Tau levels in human cerebrospinal fluid, the antibodies permitted us to discriminate patients with Alzheimer disease or other dementia like vascular dementia, indicative that these antibodies hold promising diagnostic potential.Lire moins >

Langue :

Anglais

Audience :

Non spécifiée

Projet ANR :

Développement de stratégies innovantes pour une approche transdisciplinaire de la maladie d'Alzheime

Établissement(s) :

CHU Lille
CNRS
Université de Lille
Inserm

Collections :

• Lille Neurosciences & Cognition (LilNCog) - U 1172
• Unité de Glycobiologie Structurale et Fonctionnelle (UGSF) - UMR 8576

Équipe(s) de recherche :

RMN et interactions moléculaires

Date de dépôt :

2020-02-12T15:44:58Z
2021-04-28T10:21:22Z
2021-04-28T10:25:46Z