A Novel Sensitive Method of Detecting Mnemonic Decline in Mouse Model of Alzheimer's Disease

Abstract

Deficits in transferring generalized information of past learning to new problems are related to mild hippocampal atrophy in the elderly and appear to be an early marker of age-related cognitive decline. This inability to transfer information could be used as an early diagnostic tool for such decline, and a rodent model that is sensitive to this deficit could be valuable in the search for therapies to prevent or reverse such impairments. The goal of this study is to develop an analogous animal model to be used for assessing cognitive abilities in a variety of transgenic mouse models of Alzheimer’s disease (AD). Such a rodent model will be valuable for identifying specific biomarkers associated with early age-related cognitive decline and should prove useful for developing and testing therapies directed at preventing or reversing such impairments. Three month old APP+PS1 mice were not impaired in initial discrimination learning or on the ability to ransfer this learned information to the altered context. In contrast, at 12 months of age, APP+PS1 mice learned the initial concurrent discriminations on par with iv NTgs but were impaired when required to “transfer” this learning into a new configuration/context. There were no differences in Morris water maze performance between the APP+Ps1 and NTgs at 12 months of age. These data are the first to demonstrate deficits associated with reconfiguration of stimuli or transfer learning thought to be dependent on the hippocampal formation is impaired in a mouse model of AD. Moreover, these data suggest that this deficit may precede or is more sensitive in detecting deficits than water maze in this model.