Document Detail

Reduction of amyloid angiopathy and Abeta plaque burden after enriched housing in TgCRND8 mice: involvement of multiple pathways.
MedLine Citation:
PMID:  16877355     Owner:  NLM     Status:  MEDLINE    
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.
Oliver Ambrée; Uwe Leimer; Arne Herring; Nicole Görtz; Norbert Sachser; Michael T Heneka; Werner Paulus; Kathy Keyvani
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The American journal of pathology     Volume:  169     ISSN:  0002-9440     ISO Abbreviation:  Am. J. Pathol.     Publication Date:  2006 Aug 
Date Detail:
Created Date:  2006-07-31     Completed Date:  2006-09-01     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  0370502     Medline TA:  Am J Pathol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  544-52     Citation Subset:  AIM; IM    
University Hospital Münster, Institute of Neuropathology, Domagkstr. 19, D-48149, Münster, Germany.
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MeSH Terms
Amyloid beta-Protein Precursor / metabolism*
Cerebral Amyloid Angiopathy / pathology*
Gene Expression Regulation
Glial Fibrillary Acidic Protein / metabolism
Gliosis / metabolism
Glucocorticoids / blood
Housing, Animal*
Mice, Transgenic
Microarray Analysis
Microglia / pathology
Protein Processing, Post-Translational
Senile Plaques / pathology*
Reg. No./Substance:
0/Amyloid beta-Protein Precursor; 0/Glial Fibrillary Acidic Protein; 0/Glucocorticoids

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