title: Preventive and therapeutic types of environmental enrichment counteract beta amyloid pathology by different molecular mechanisms.
abstract: Combined preventive and therapeutic physical/cognitive stimulation starting before disease onset and continuing over its progression reduce Alzheimer-related pathology in transgenic mice. We now report that exposure of TgCRND8 mice to an enriched environment as either a preventive or therapeutic approach is also capable to reduce Aβ burden, though with different plaque and cerebral amyloid angiopathy (CAA) morphology. Preventive treatment resulted in fewer and smaller plaques without affecting CAA, whereas in therapeutically treated mice beside reduction of CAA extent, numerous plaques of strongly diminished size were found, so that total plaque loads declined as well. These effects seemed to be mediated by distinct molecular pathways. In preventive but not therapeutic group a shift of Aβ(42/40) ratio towards Aβ(40) and up-regulation of Aβ clearing and degrading molecules were found. Contrariwise anti-oxidative defense mechanisms were induced only in therapy but not preventive group. We hypothesize that preventive enrichment lowers the amounts of plaque seeds and decelerates plaque growth by degradation and clearance of Aβ, while therapeutic enrichment mitigates growth and fusion of plaque seeds to large plaques by inhibiting further Aβ aggregation. This study provides an experimental basis for application of physical/cognitive training in both prophylaxis and therapy of Alzheimer's disease.
authors.affiliation: Institute of Pathology and Neuropathology, University Hospital Essen, Hufelandstr 55, 45122 Essen, Germany. arne.herring@uk-essen.de
authors.forename: Arne
authors.initials: A
authors.lastname: Herring
authors.forename: Lars
authors.initials: L
authors.lastname: Lewejohann
authors.forename: Anna-Lena
authors.initials: AL
authors.lastname: Panzer
authors.forename: Anja
authors.initials: A
authors.lastname: Donath
authors.forename: Oliver
authors.initials: O
authors.lastname: Kröll
authors.forename: Norbert
authors.initials: N
authors.lastname: Sachser
authors.forename: Werner
authors.initials: W
authors.lastname: Paulus
authors.forename: Kathy
authors.initials: K
authors.lastname: Keyvani
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000704:Analysis of Variance; D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology*; D004195:Disease Models, Animal; D018450:Disease Progression; D004777:Environment; D005260:Female; D007150:Immunohistochemistry; D051379:Mice; D008822:Mice, Transgenic; D058225:Plaque, Amyloid / Q000378:metabolism / Q000473:pathology*; D018709:Statistics, Nonparametric
chemical_list: D016229:Amyloid beta-Peptides