Observations in THY-Tau22 mice that resemble behavioral and psychological signs and symptoms of dementia

Abstract

THY-Tau22 mice constitute an animal model for tau aggregation, a hallmark in Alzheimer's disease (AD) and Tauopathies. Our previous studies have shown learning and memory deficits and changes in synaptic plasticity in the hippocampus in THY-Tau22 mice that are consistent with the learning impairments seen in AD-patients. However, behavioral disturbances are the most important problems in the management of AD and are major determinants of nursing home placement. Thus, we hypothesized that THY-Tau22 mice would demonstrate, in addition to the cognitive impairments, at least some behavioral and psychological signs and symptoms of dementia (BPSD). We found that 12 months old THY-Tau22 mice, relative to wild-type (WT) littermates display increased depression-like and aggressive behavior, co-occurring with disturbances in nocturnal activity. Moreover, these changes were linked to a decreased hippocampal concentration in serotonin, or 5-hydroxytryptamine (5-HT), and 5-hydroxyindoleacetic acid (5-HIAA), the main metabolite of serotonin. Together these data corroborate the usefulness of the model in preclinical evaluations of therapeutic strategies that aim to reverse cognitive defects and alleviate BPSD in the human disease.