Enriched physical environment reverses spatial cognitive impairment of socially isolated APPswe/PS1dE9 transgenic mice before amyloidosis onset.

Social isolation increases the onset of Alzheimer's disease (AD). Environmental enrichment, a complicated social and physical construct, plays beneficial effects on brain plasticity and function. This study was designed to determine whether physical enrichment can reduce the deleterious consequences of social isolation on the onset of AD. One-month-old APPswe/PS1dE9 transgenic AD model mice were singly housed in the enriched physical environment for 8 weeks and then received behavioral tests, neuropathological analyses, and Western blot of the hippocampus. The enriched physical environment reversed spatial cognitive decline of socially isolated APPswe/PS1dE9 mice. The functional reversal was associated with decreases in cellular apoptosis, synaptic protein loss, inflammation, and glial activation in the hippocampus, without changes in amyloid β neuropathology. These results suggest that the enriched physical environment may serve as a nonpharmacological intervention for delaying the onset of AD accompanied with social isolation.