Prevention of tau seeding and propagation by immunotherapy with a central tau epitope antibody
Rattachement africain : fr, be. Niveau de preuve : code pays fourni par la source.
Le résumé fourni par la source
Tauopathies are neurodegenerative diseases characterized by the intraneuronal accumulation of aggregated tau. The staging of this neurodegenerative process is well established for Alzheimer's disease as well as for other tauopathies. The stereotypical pattern of tau pathology in these diseases is consistent with the hypothesis that the tau protein can spread in a 'prion-like' manner. It proposes that extracellular pathological tau species can transmit pathology from cell to cell. Accordingly, by targeting these spreading species with therapeutic antibodies one should be able to slow or halt the progression of tau pathology. To be effective, antibodies should neutralize the pathological species present in Alzheimer's disease brains and block their cell-to-cell spread. To evaluate both aspects, tau antibody D, which recognizes an epitope in the central region of tau, and was selected for its outstanding ability to block tau seeding in cell based assays, was used in this study. Here, we addressed two fundamental questions: (i) can this anti-tau antibody neutralize the pathological species present in Alzheimer's disease brains; and (ii) can it block the cell-to-cell spread of tau seeds in vivo? First, antibody D effectively prevented the induction of tau pathology in the brains of transgenic mice that had been injected with human Alzheimer's disease brain extracts, showing that it could effectively neutralize the pathological species present in these extracts. Second, by using K18 P301L tau fibrils to induce pathology, we further demonstrated that antibody D was also capable of blocking the progression of tau pathology to distal brain regions. In contrast, an amino-terminal tau antibody, which was less effective at blocking tau seeding in vitro showed less efficacy in reducing Alzheimer's disease patient tau driven pathology in the transgenic mouse model. We did not address whether the same is true for a spectrum of other amino-terminal antibodies that were tested in vitro. These data highlight important differences between tau antibodies and, when taken together with other recently published data, suggest that epitope may be important for function.
Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.
Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Prevention of tau seeding and propagation by immunotherapy with a central tau epitope antibody
- Date Crossref
- 30/04/2019
- Éditeur
- Oxford University Press (OUP)
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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Inserm pays non établi dans la noticeOrganisme public
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Université de Lille pays non établi dans la noticeUniversité ou école supérieure
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Lille Neurosciences & Cognition pays non établi dans la noticeStructure de recherche
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UCB Pharma (Belgium) pays non établi dans la noticeEntreprise
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Centre National de la Recherche Scientifique pays non établi dans la noticeOrganisme public
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Centre Hospitalier Universitaire de Lille pays non établi dans la noticeÉtablissement de santé
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UCB Biopharma pays non établi dans la noticeInstitution
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CNRS pays non établi dans la noticeStructure de recherche
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CHU-Lille pays non établi dans la noticeÉtablissement de santé
Inserm, Université de Lille et Lille Neurosciences & Cognition, avec 6 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.