Behavioural and psychological symptoms of dementia in mouse models of Alzheimer's disease-related pathology

Abstract

Transgenic mouse models have been used extensively to model the cognitive impairments arising from Alzheimer's disease (AD)-related pathology. However, less is known about the relationship between AD-related pathology and the behavioural and psychological symptoms of dementia (BPSD) commonly presented by patients. This review discusses the BPSD-like behaviours recapitulated by several mouse models of AD-related pathology, including the APP/PS1, Tg2576, 3xTg-AD, 5xFAD, and APP23 models. Current evidence suggests that social withdrawal and depressive-like behaviours increase with progressive neuropathology, and increased aggression and sleep-wake disturbances are present even at early stages; however, there is no clear evidence to support increased anxiety-like behaviours, agitation (hyperactivity), or general apathy. Overall, transgenic mouse models of AD-related pathology recapitulate some of the BPSD-like behaviours associated with AD, but these behaviours vary by model. This reflects the patient population, where AD patients typically exhibit one or more BPSD, but rarely all symptoms at once. As a result, we suggest that transgenic mouse models are an important tool to investigate the pathology underlying BPSD in human AD patients.

Keywords: Alzheimer’s disease; Amyloid; Behavioral and psychological symptoms of dementia (BPSD); Mouse models; Neuropsychiatric symptoms (NPS); Social behaviours; Tau.