title: Reduction of amyloid angiopathy and Abeta plaque burden after enriched housing in TgCRND8 mice: involvement of multiple pathways.
abstract: 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.
authors.affiliation: University Hospital Münster, Institute of Neuropathology, Domagkstr. 19, D-48149, Münster, Germany.
authors.forename: Oliver
authors.initials: O
authors.lastname: Ambrée
authors.forename: Uwe
authors.initials: U
authors.lastname: Leimer
authors.forename: Arne
authors.initials: A
authors.lastname: Herring
authors.forename: Nicole
authors.initials: N
authors.lastname: Görtz
authors.forename: Norbert
authors.initials: N
authors.lastname: Sachser
authors.forename: Michael T
authors.initials: MT
authors.lastname: Heneka
authors.forename: Werner
authors.initials: W
authors.lastname: Paulus
authors.forename: Kathy
authors.initials: K
authors.lastname: Keyvani
mesh_terms: D016564:Amyloid beta-Protein Precursor / Q000378:metabolism*; D000818:Animals; D016657:Cerebral Amyloid Angiopathy / Q000473:pathology*; D005260:Female; D005786:Gene Expression Regulation; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D005911:Gliosis / Q000378:metabolism; D005938:Glucocorticoids / Q000097:blood; D006799:Housing, Animal; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D046228:Microarray Analysis; D017628:Microglia / Q000473:pathology; D058225:Plaque, Amyloid / Q000473:pathology*; D011499:Protein Processing, Post-Translational; D012995:Solubility
chemical_list: D016564:Amyloid beta-Protein Precursor; D005904:Glial Fibrillary Acidic Protein; D005938:Glucocorticoids