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Htau mice are deficient of murine tau but express all six human tau isoforms, leading to gradual tau misprocessing and aggregation in brain areas relevant to Alzheimer’s disease. Whilst histopathological changes in htau mice have been researched in the past, we focused here on functional consequences of human tau accumulation.htau mice and their background controls murine tau knock out (mtau / ) and C57Bl/6J mice underwent a comprehensive trial battery to investigate species specific behaviour, locomotor activity, emotional responses, exploratory traits, spatial and recognition memory as well as acquisition, retention and extinction of contextual fear at two , four , six , nine and twelve months of age.In htau mice, tau pathology was already present at two months of age, whereas deficits in food burrowing and spatial working memory were first noted at four months of age. At later stages the presence of human tau on a murine tau knockout background appeared to guard cognitive performance; as mtau / but not htau mice differed from C57Bl/6J mice in the food burrowing, spontaneous alternation and object discrimination tasks.