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

• Published in: Acta neuropathologica communications Vol. 12; no. 1; p. 52
• Main 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
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 04.04.2024; BioMed Central; BioMed Central part of Springer Science; BMC
• Series: Acta Neuropathologica Communications
• Subjects: Aggregation; Alzheimer Disease - pathology; Alzheimer's disease; Animal models; Animals; Brain; Brain - pathology; Dementia; Disease Models, Animal; Drug therapy; Life Sciences; Neurofibrillary tangles; Neurofibrillary Tangles - pathology; Pathology; Propagation; Proteins; Review; Spreading; Tau protein; tau Proteins - metabolism; Tauopathies - pathology; Aggregation; Animal models; Neurofibrillary tangles; Propagation; Tau protein; Spreading
• ISSN: 2051-5960; 2051-5960
• DOI: 10.1186/s40478-024-01748-5

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.