Fig. 2

Inoculation-based tau propagation models. The graphical abstract illustrates the pivotal elements highlighted in this review. The central theme revolves around the transcellular propagation of aberrantly modified tau protein along the functional brain network. The depicted framework emphasizes the critical steps for establishing robust models, including the judicious selection and comprehensive characterization of tau inocula through functional, biochemical, and biophysical analyses (1, 2). Key considerations involve the careful choice of animal models (3), optimal inoculation sites (4), the crucial validation of fibrillary pathology using confirmatory staining techniques (5) and downstream assessment (6). The proposed framework serves as a practical guide for researchers, offering a systematic approach to establish benchmark models for preclinical testing of potential disease-modifying drugs (DMTs)