Anti-Tau Monoclonal Antibodies Derived from Soluble and Filamentous Tau Show Diverse Functional Properties in vitro and in vivo

Marc Vandermeeren, Marianne Borgers, Kristof Van Kolen*, Clara Theunis, Bruno Vasconcelos, Astrid Bottelbergs, Cindy Wintmolders, Guy Daneels, Roland Willems, Koen Dockx, Lore Delbroek, Andre Marreiro, Luc Ver Donck, Cristiano Sousa, Rupesh Nanjunda, Eilyn Lacy, Tom Van de Casteele, Debby Van Dam, Peter Paul De Deyn, John A. KempThomas J. Malia, Marc H. Mercken

*Bijbehorende auteur voor dit werk

OnderzoeksoutputAcademicpeer review

27 Citaten (Scopus)

Samenvatting

The tau spreading hypothesis provides rationale for passive immunization with an anti-tau monoclonal antibody to block seeding by extracellular tau aggregates as a disease-modifying strategy for the treatment of Alzheimer's disease (AD) and potentially other tauopathies. As the biochemical and biophysical properties of the tau species responsible for the spatio-temporal sequences of seeding events are poorly defined, it is not yet clear which epitope is preferred for obtaining optimal therapeutic efficacy. Our internal tau antibody collection has been generated by immunizations with different tau species: aggregated-and non-aggregated tau and human postmortem AD brain-derived tau fibrils. In this communication, we describe and characterize a set of these anti-tau antibodies for their biochemical and biophysical properties, including binding, tissue staining by immunohistochemistry, and epitope. The antibodies bound to different domains of the tau protein and some were demonstrated to be isoform-selective (PT18 and hTau56) or phospho-selective (PT84). Evaluation of the antibodies in cellular-and in vivo seeding assays revealed clear differences in maximal efficacy. Limited proteolysis experiments support the hypothesis that some epitopes are more exposed than others in the tau seeds. Moreover, antibody efficacy seems to depend on the structural properties of fibrils purified from tau Tg mice-and postmortem human AD brain.

Originele taal-2English
Pagina's (van-tot)265-281
Aantal pagina's17
TijdschriftJournal of alzheimers disease
Volume65
Nummer van het tijdschrift1
DOI's
StatusPublished - 2018

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