Abstract
Tauopathies are neurodegenerative diseases characterized by pathological tau protein inclusions and dementia. Tauopathy mouse models with MAPT mutations replicate tau-related pathologies and are widely used for therapeutic research. This scoping review examines 409 treatment evaluations in MAPT mouse models. We identify trends in therapeutic strategies and frequently used mouse models, treatment routes, and endpoints. We also document treatment effects and when treatment is initiated relative to tau pathology emergence. Many treatments produced positive effects in multiple MAPT mouse models across many endpoints but showed limited success in clinical trials. Potential barriers to mouse-to-human translation include differences between mouse and human studies in the timing of treatment initiation relative to tau pathology onset, predominant testing of a limited number of endpoints, lack of translatable treatment response biomarkers, and the limited ability of individual mouse models to represent the diversity of tauopathies. Addressing these obstacles could improve mouse-to-human translation for tauopathy therapeutics. HIGHLIGHTS: Two decades of therapeutic research in tauopathy mouse models were reviewed. Treatments often began before or at tau pathology onset in tauopathy mouse models. Key endpoints (e.g., cognition and synaptic degeneration) were underassessed. Well-characterized preclinical treatments often had limited success in humans. Single-sex mouse studies and a lack of biomarkers hinder clinical translation.