Age and gene overexpression interact to abolish nesting behavior in Tg2576 amyloid precursor protein (APP) mice

Elucidating the modulators of social behavioral is important in understanding the neural basis of behavior and in developing methods to enhance behavior in cases of disorder. The work here stems from the observation that the Alzheimer's disease mouse model Tg2576, overexpressing human mutations of the amyloid-β precursor protein (APP), fails to construct nests when supplied paper towels in their home cages. Experiments using commercially available cotton nesting material found similar results. Additional experiments revealed that the genotype effect is progressively modulated by age in APP mice but not their WT counterparts. There was no effect of sex on nesting behavior in any group. Finally, this effect was independent of ambient temperature – even when subjected to a cold environment, APP mice fail to build nests whereas WT mice do. These results suggest that the APP gene plays a role in affiliative behaviors and are discussed in relation to disorders characteristic of mutations in the APP gene and in affective dysfunction, including Alzheimer's disease.

Research highlights▶ Construction of nests is an affiliative behavior influenced by numerous factors. Mice overexpressing mutant amyloid precursor protein (APP) fail to construct nests. ▶ Nest building in APP mice becomes progressively worse from 2 to 20 months of age. ▶ These results suggest that APP expression modulates nest construction.