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(American Journal of Pathology. 2006;169:544-552.)
© 2006 American Society for Investigative Pathology
DOI: 10.2353/ajpath.2006.051107

Reduction of Amyloid Angiopathy and Aß Plaque Burden after Enriched Housing in TgCRND8 Mice

Involvement of Multiple Pathways

Oliver Ambrée*{dagger}, Uwe Leimer{ddagger}, Arne Herring*, Nicole Görtz{dagger}, Norbert Sachser{dagger}, Michael T. Heneka{ddagger}, Werner Paulus* and Kathy Keyvani*

From the Institute of Neuropathology* and the Department of Molecular Neurology,{ddagger} University Hospital Münster, Münster; and the Department of Behavioural Biology,{dagger} University of Münster, Münster, Germany

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 TgCRND8 mice carrying human APPswe+ind were transferred into enriched housing. Four months of continuous and diversified environmental stimulation resulted in a significant reduction of ß-amyloid (Aß) 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 Aß content differed between both groups, making alterations in APP expression or processing unlikely as a cause of reduced Aß deposition. Moreover, DNA microarray analysis revealed simultaneous down-regulation of proinflammatory genes as well as up-regulation of molecules involved in anti-inflammatory processes, proteasomal degradation, and cholesterol binding, possibly explaining reduced Aß burden by lower aggregation and enhanced clearance of Aß. 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 dif-ferent levels.








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Copyright © 2006 by the American Society for Investigative Pathology.