[en] 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 beta-amyloid (Abeta) 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 Abeta content differed between both groups, making alterations in APP expression or processing unlikely as a cause of reduced Abeta 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 Abeta burden by lower aggregation and enhanced clearance of Abeta. 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.
Disciplines :
Neurology
Author, co-author :
Ambrée, Oliver; University Hospital Münster, Institute of Neuropathology, Domagkstr. 19, D-48149, Münster, Germany
Leimer, Uwe; Department of Molecular Neurology, University Hospital Münster, Münster, Germany
Herring, Arne; Institute of Neuropathology, University Hospital Münster, Münster, Germany
Görtz, Nicole; Department of Behavioural Biology, University of Münster, Münster, Germany
Sachser, Norbert; Department of Behavioural Biology, University of Münster, Münster, Germany
HENEKA, Michael ; Department of Molecular Neurology, University Hospital Münster, Münster, Germany
Paulus, Werner; Institute of Neuropathology, University Hospital Münster, Münster, Germany
Keyvani, Kathy; Institute of Neuropathology, University Hospital Münster, Münster, Germany ; University Hospital Münster, Institute of Neuropathology, D-48149, Münster, Germany
External co-authors :
yes
Language :
English
Title :
Reduction of amyloid angiopathy and Abeta plaque burden after enriched housing in TgCRND8 mice: involvement of multiple pathways.
Publication date :
August 2006
Journal title :
American Journal of Pathology
ISSN :
0002-9440
eISSN :
1525-2191
Publisher :
American Society for Investigative Pathology Inc., United States
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