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The ε4 allele of apolipoprotein E (apoE4) is the predominant genetic risk factor for late‐onset Alzheimer's disease (AD) and is also implicated in cognitive deficits associated with normal aging. The biological mechanisms by which APOE genotype affects cognitive processes or AD pathogenesis remain unclear, but interactions of apoE with amyloid β peptide (Aβ) are thought to play an important role in mediating apoE's isoform‐specific effects on brain function. Here, we investigated the potential isoform‐dependent effects of apoE on behavioral and cognitive performance in human apoE3 and apoE4 targeted‐replacement (TR) mice that also overexpress the human amyloid precursor protein (APP). Beginning at 6–7 months of age, female APP‐Yac/apoE3‐TR (‘poE3’) and APP‐Yac/apoE4‐TR (‘poE4’) mice were tested on a battery of tests to evaluate basic sensorimotor functioning, spatial working memory, spatial recognition, episodic‐like memory and attentional processing. Compared with apoE3 mice, a generalized reduction in locomotor activity was observed in apoE4 mice. Moderate, but significant, cognitive impairments were also detected in apoE4 mice in the novel object‐location preference task, the contextual fear conditioning test, and a two‐choice visual discrimination/detection test, however spontaneous alternation performance in the Y‐maze was spared. These results offer additional support for the negative impact of apoE4 on both memory and attention and further suggest that APP‐Yac/apoE‐TR mice provide a novel and useful model for investigating the role of apoE in mediating susceptibility to cognitive decline....
Sustained attention is defined as the ability or capacity to remain focused on the occurrence of rare events over long periods of time. We describe here the development of a novel, operant-based attention task that can be learned by mice in 8–10 days. Mice were trained on a 2-choice visual discrimination task in an operant chamber, wherein the correct response on any given trial was a lever-press...
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