Novel Behavioural Characteristics of Male Human P301S Mutant Tau Transgenic Mice – A Model for Tauopathy

Alzheimer's disease (AD) is a neurodegenerative disease characterised by progressive cognitive decline and the accumulation of two hallmark proteins, amyloid-beta (Aβ) and tau. Traditionally, transgenic mouse models for AD have generally focused on Aβ pathology, however, in recent years a number of tauopathy transgenic mouse models have been developed, including the TAU58/2 mouse model. These mice develop tau pathology and neurofibrillary tangles from 2 months of age and show motor impairments and alterations in the behavioural response to elevated plus maze (EPM) testing. The cognitive and social phenotype of this model has not yet been assessed comprehensively. Furthermore, the behavioural changes seen in the EPM have previously been linked to both anxiety and disinhibitory phenotypes. Thus, this study assessed 4-month-old TAU58/2 males comprehensively for disinhibitory and social behaviours, social recognition memory, and sensorimotor gating. TAU58/2 males demonstrated reduced exploration and anxiety-like behaviours but no changes to disinhibitory behaviours, reduced sociability in the social preference test and impaired acoustic startle and prepulse inhibition. Aggressive and socio-positive behaviours were not affected except a reduction in the occurrence of nosing and anogenital sniffing. Our study identified new phenotypic characteristics of young adult male TAU58/2 transgenic mice and clarified the nature of changes detected in the behavioural response of these mice to EPM testing. Social withdrawal and inappropriate social behaviours are common symptoms in both AD and FTD patients and impaired sensorimotor gating is seen in moderate-late stage AD, emphasising the relevance of the TAU58/2 model to these diseases.