The "Swedish" mutation of the amyloid precursor protein (APPswe) dissociates components of object-location memory in aged Tg2576 mice.

Aged Tg2576 mice show abnormalities in hippocampal morphology and physiology and display behavioral deficits in spatial navigation tasks consonant with a deficit in the functional properties of the hippocampus. However, the nature of the spatial representations disrupted by the "Swedish" mutation of the amyloid precursor protein (APPswe) is unclear. In an effort to characterize the memory deficits in Tg2576 mice, the spontaneous object exploration paradigm was used to interrogate spatial and object memory in mice. With object arrays of comparable size, 16-month-old Tg2576 mice showed a normal object familiarity/novelty effect but impaired memory for the location of objects when 2 objects exchanged locations (topological transformation; Experiment 1). In contrast, Tg2576 mice showed preferential exploration of familiar objects when they were moved to previously unoccupied locations (Experiment 2), irrespective of whether the transformation altered the metric properties of the object array (Experiments 3). These results suggest that Tg2576 mice are able to form representations of the identity of objects and a memory of the spatial organization of objects in an arena. In contrast, conjunctive memory for specific object-location associations is severely impaired in aged Tg2576 mice.

Impaired "episodic-like" object memory in adult APPswe transgenic mice.

An early clinical symptom of Alzheimer's disease is impaired episodic memory. However, the precise pathological event(s) that underpins this deficit remains unclear. In the present study, the authors examined whether wild-type mice and Tg2576 mice expressing an amyloid precursor protein (APP) mutation are able to form an integrated memory of the spatio-temporal context in which objects are presented. In Experiment 1, wild-type mice, but not Tg2576 mice that were 10-12 months old, explored objects presented in a novel location. In Experiment 2, wild-type mice explored an object that was presented both earlier in a sequence and in a different location relative to other objects that possessed only one of these properties (i.e., memory for "what," "where," and "when" items were presented). In contrast, the behavior of adult Tg2576 mice was influenced only by the temporal order in which objects were presented. These results demonstrate that wild-type, but not APP-mutant, mice are able to form an "episodic-like" memory of the spatio-temporal properties of objects and support the hypothesis that aberrant APP processing contributes to impairments in event memory.

Impaired visuospatial recognition memory but normal object novelty detection and relative familiarity judgments in adult mice expressing the APPswe Alzheimer's disease mutation.

The present study examined the effects of a human APPswe mutation on object recognition memory in adult Tg2576 mice. The results showed that 14-month old Tg2576 mice were able to detect object novelty as well as control mice, even with delays of up to 24 hr. In addition, transgenic mice showed a normal recency effect and explored the most recently encountered object significantly less than an object encountered earlier in a trial. However, adult Tg2576 mice showed impairments in detecting a change in the relative positions of an array of familiar objects. The results suggest that the formation of representations involving a combination of object identity and spatial information are particularly sensitive to amyloid pathology in adult APPswe mutant mice.

Intramaze and extramaze cue processing in adult APPSWE Tg2576 transgenic mice.

The present study examined spatial and nonspatial learning in adult Tg2576 mice. Transgenic mice were impaired in acquisition of a T-maze forced-choice alternation task. However, mutant mice were as sensitive as control mice to the introduction of retention intervals and proactive interference, and this suggested that short-term memory processes were intact in Tg2576 mice. Probe trials revealed that the Tg2576 mice did not use an allocentric strategy to navigate to the goal arm. However, mutant mice acquired an intramaze brightness discrimination, a simple room discrimination, and a contextual biconditional left-right discrimination in a T maze. Results suggest that Tg2576 mice are able to process both intramaze and extramaze stimuli but are impaired in forming an allocentric representation of their environment.