Spatial Disorientation Under Dark Conditions Across Development in an Alzheimer’s Disease Mouse Model

Abstract

Alzheimer’s disease (AD) is associated with hippocampal neuropathology and cognitive impairments, including wandering behavior or becoming lost in a familiar environment. Wandering behavior is severe and manifests early in life for people with specific genetic mutations. Genetic mouse models of AD have been developed to characterize the onset and progression of behavioral deficits that represent human behaviors, such as wandering, to test the efficacy of therapeutics. It is not clear if current assessments of mouse models capture the onset of AD or a snapshot of its progression. Sequential analysis of open field behavior provides a robust, quick test to dissociate navigation cues that contribute to spatial disorientation, a feature of wandering. Despite potential utility in evaluating this feature of AD, little work has been reported using animal models of dementia in this task. Thus, we examined the use of different sources of information to maintain spatial orientation at two prodromal ages in female transgenic CRND8 AD (n = 17) and Control mice (n = 16). These mice exhibit amyloid plaques, a hallmark neuropathological feature of AD, that are associated with cognitive dysfunction at ∼three months of age. Spatial disorientation was observed at two months and more severely at four months under dark conditions, but performance was spared when visual environmental cues were available. This study provides documentation of impaired self-movement cue processing in AD mice, establishing the dark open field as a behavioral tool to characterize spatial disorientation associated with AD. These findings may accelerate future assessments of novel therapeutic interventions for neurological disorders.