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

Investor logo

Warning

This publication doesn't include Faculty of Sports Studies. It includes Faculty of Science. Official publication website can be found on muni.cz.
Authors

BASHEER Neha BUEE Luc BRION Jean-Pierre SMOLEK Tomas MUHAMMADI Muhammad Khalid HRITZ Jozef HROMADKA Tomas DEWACHTER Ilse WEGMANN Susanne LANDRIEU Isabelle NOVAK Petr MUDHER Amritpal ZILKA Norbert

Year of publication 2024
Type Article in Periodical
Magazine / Source Acta Neuropathologica Communications
MU Faculty or unit

Faculty of Science

Citation
Web https://actaneurocomms.biomedcentral.com/articles/10.1186/s40478-024-01748-5
Doi http://dx.doi.org/10.1186/s40478-024-01748-5
Keywords Tau protein; Propagation; Spreading; Aggregation; Neurofibrillary tangles; Animal models
Description 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.
Related projects:

You are running an old browser version. We recommend updating your browser to its latest version.

More info