Comparing the Spatiotemporal Progression of Tau Pathology Across Transgenic Mouse Models Relevant to Alzheimer's Disease: A Structured Review

Tau pathology is closely linked to cognitive decline in Alzheimer's disease, but the way it progresses can look very different depending on the mouse model being studied. This review compares five commonly used transgenic mouse models to examine where tau pathology first appears, how it progresses through the brain, and how closely that progression resembles what is seen in human Alzheimer's disease. The models included were rTgTauEC, 3xTg-AD, PS19 (P301S), rTg4510, and APPswe/PS1ΔE9. Across the studies, tau pathology became more extensive over time, although the patterns differed between models. Evidence from rTgTauEC and broader connectivity analyses suggested that neural connections may influence how tau pathology spreads through the brain. rTgTauEC showed the strongest resemblance to early Braak-like progression, with pathology beginning in the entorhinal cortex and later appearing in connected hippocampal regions. The other models captured different parts of the disease. 3xTg-AD was useful for looking at amyloid and tau together, while PS19 and rTg4510 developed more extensive tau pathology and neurodegeneration. APPswe/PS1ΔE9 was different because its tau abnormalities appeared mainly in association with amyloid pathology. The main finding of this review is that there is not one mouse model that accurately represents every stage of tau progression in Alzheimer's disease. Each model answers a slightly different question. Understanding those differences is important when deciding which model is most appropriate for studying tau pathology or testing a potential treatment.