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Published in: Acta Neuropathologica Communications 1/2024

Open Access 01-12-2024 | Alzheimer's Disease | Review

Shaping the future of preclinical development of successful disease-modifying drugs against Alzheimer's disease: a systematic review of tau propagation models

Authors: Neha Basheer, Luc Buee, Jean-Pierre Brion, Tomas Smolek, Muhammad Khalid Muhammadi, Jozef Hritz, Tomas Hromadka, Ilse Dewachter, Susanne Wegmann, Isabelle Landrieu, Petr Novak, Amritpal Mudher, Norbert Zilka

Published in: Acta Neuropathologica Communications | Issue 1/2024

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Abstract

The transcellular propagation of the aberrantly modified protein tau along the functional brain network is a key hallmark of Alzheimer's disease and related tauopathies. Inoculation-based tau propagation models can recapitulate the stereotypical spread of tau and reproduce various types of tau inclusions linked to specific tauopathy, albeit with varying degrees of fidelity. With this systematic review, we underscore the significance of judicious selection and meticulous functional, biochemical, and biophysical characterization of various tau inocula. Furthermore, we highlight the necessity of choosing suitable animal models and inoculation sites, along with the critical need for validation of fibrillary pathology using confirmatory staining, to accurately recapitulate disease-specific inclusions. As a practical guide, we put forth a framework for establishing a benchmark of inoculation-based tau propagation models that holds promise for use in preclinical testing of disease-modifying drugs.
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Metadata
Title
Shaping the future of preclinical development of successful disease-modifying drugs against Alzheimer's disease: a systematic review of tau propagation models
Authors
Neha Basheer
Luc Buee
Jean-Pierre Brion
Tomas Smolek
Muhammad Khalid Muhammadi
Jozef Hritz
Tomas Hromadka
Ilse Dewachter
Susanne Wegmann
Isabelle Landrieu
Petr Novak
Amritpal Mudher
Norbert Zilka
Publication date
01-12-2024
Publisher
BioMed Central
Published in
Acta Neuropathologica Communications / Issue 1/2024
Electronic ISSN: 2051-5960
DOI
https://doi.org/10.1186/s40478-024-01748-5

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