Institute of Neuroimmunology, Slovak Academy of Sciences, Dubravska Cesta 9, 845 10, Bratislava, Slovakia.
Inserm, CHU Lille, CNRS, LilNCog - Lille Neuroscience & Cognition, University of Lille, 59000, Lille, France.
Acta Neuropathol Commun. 2024 Apr 4;12(1):52. 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.
异常修饰的蛋白 tau 沿着功能大脑网络的细胞间传播是阿尔茨海默病和相关 tau 病的一个关键标志。基于接种的 tau 传播模型可以重现 tau 的典型传播，并再现与特定 tau 病相关的各种 tau 包含物，尽管具有不同程度的保真度。通过这项系统评价，我们强调了明智选择和细致的功能、生化和生物物理特性分析各种 tau 接种物的重要性。此外，我们还强调了选择合适的动物模型和接种部位的必要性，以及使用确认性染色验证纤维状病理学的必要性，以准确再现疾病特异性包含物。作为实用指南，我们提出了一个建立基于接种的 tau 传播模型基准的框架，该框架有望用于疾病修饰药物的临床前测试。
