Prolonged Isolation Stress Accelerates the Onset of Alzheimer's Disease-Related Pathology in 5xFAD Mice Despite Running Wheels and Environmental Enrichment.

•Two and three months of social isolation lead to cognitive deficits in a CFC paradigm in 5xFAD+ and wild-type animals.•Two and three months of social isolation lead to increased plaques in the hippocampus of 5xFAD + mice.•Three months of isolation increased hippocampal BACE1 expression in 5xFAD + and wild-type animals.•These effects cannot be prevented by exercise or exercise and an enriched environment during 3 months of isolation.