Reduction of amyloid angiopathy and Aβ plaque burden after enriched housing in TgCRND8 mice -: Involevement of multiple pathways

Diversity and intensity of intellectual and physical activities seem to have an inverse relationship with the extent of cognitive decline in Alzheimer's disease (AD). To study the interaction between an active lifestyle and AD pathology, female TgCRND(8) mice carrying human APPswe+ind were transferred into enriched housing. Four months of continuous and diversified environmental stimulation resulted in a significant reduction of beta-amyloid (A beta) plaques and in a lower extent of amyloid angiopathy. Neither human amyloid precursor protein (APP) mRNA/protein levels nor the level of carboxy-terminal fragments of APP nor soluble A,6 content differed between both groups, making alterations in APP expression or processing unlikely as a cause of reduced A beta deposition. Moreover, DNA microarray analysis revealed simultaneous down-regulation of proinflammatory genes as well as up-regulation of molecules involved in antiinflammatory processes, proteasomal degradation, and cholesterol binding, possibly explaining reduced A,6 burden by lower aggregation and enhanced clearance of A beta. Additionally, immunoblotting; against F4/80 antigen and morphometric analysis of microglia (Mac-3) revealed significantly elevated microgliosis in the enriched brains, which suggests increased amyloid phagocytosis. In summary, this study demonstrates that the environment interacts with AD pathology at different levels.