title: A spectrum of exercise training reduces soluble Aβ in a dose-dependent manner in a mouse model of Alzheimer's disease.
abstract: Physical activity has long been hypothesized to influence the risk and pathology of Alzheimer's disease. However, the amount of physical activity necessary for these benefits is unclear. We examined the effects of three months of low and high intensity exercise training on soluble Aβ40 and Aβ42 levels in extracellular enriched fractions from the cortex and hippocampus of young Tg2576 mice. Low (LOW) and high (HI) intensity exercise training animals ran at speeds of 15m/min on a level treadmill and 32 m/min at a 10% grade, respectively for 60 min per day, five days per week, from three to six months of age. Sedentary mice (SED) were placed on a level, non-moving, treadmill for the same duration. Soleus muscle citrate synthase activity increased by 39% in the LOW group relative to SED, and by 71% in the HI group relative to LOW, indicating an exercise training effect in these mice. Soluble Aβ40 concentrations decreased significantly in an exercise training dose-dependent manner in the cortex. In the hippocampus, concentrations were decreased significantly in the HI group relative to LOW and SED. Soluble Aβ42 levels also decreased significantly in an exercise training dose-dependent manner in both the cortex and hippocampus. Five proteins involved in Aβ clearance (neprilysin, IDE, MMP9, LRP1 and HSP70) were elevated by exercise training with its intensity playing a role in each case. Our data demonstrate that exercise training reduces extracellular soluble Aβ in the brains of Tg2576 mice in a dose-dependent manner through an up-regulation of Aβ clearance.
authors.affiliation: Department of Biomedical Sciences, Missouri State University, Springfield, MO 65897, USA.
authors.forename: Kaitlin M
authors.initials: KM
authors.lastname: Moore
authors.affiliation: Department of Biomedical Sciences, Missouri State University, Springfield, MO 65897, USA.
authors.forename: Renee E
authors.initials: RE
authors.lastname: Girens
authors.affiliation: Department of Biomedical Sciences, Missouri State University, Springfield, MO 65897, USA.
authors.forename: Sara K
authors.initials: SK
authors.lastname: Larson
authors.affiliation: Department of Biomedical Sciences, Missouri State University, Springfield, MO 65897, USA.
authors.forename: Maria R
authors.initials: MR
authors.lastname: Jones
authors.affiliation: Department of Neurology, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Jessica L
authors.initials: JL
authors.lastname: Restivo
authors.affiliation: Department of Neurology, Washington University School of Medicine, St. Louis, MO 63110, USA; Hope Center, Washington University School of Medicine, St. Louis, MO 63110, USA; Alzheimer's Disease Research Center, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: David M
authors.initials: DM
authors.lastname: Holtzman
authors.affiliation: Department of Neurology, Washington University School of Medicine, St. Louis, MO 63110, USA; Hope Center, Washington University School of Medicine, St. Louis, MO 63110, USA; Alzheimer's Disease Research Center, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: John R
authors.initials: JR
authors.lastname: Cirrito
authors.affiliation: Department of Neurology, Washington University School of Medicine, St. Louis, MO 63110, USA; Hope Center, Washington University School of Medicine, St. Louis, MO 63110, USA; Alzheimer's Disease Research Center, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Carla M
authors.initials: CM
authors.lastname: Yuede
authors.affiliation: Department of Biomedical Sciences, Missouri State University, Springfield, MO 65897, USA.
authors.forename: Scott D
authors.initials: SD
authors.lastname: Zimmerman
authors.affiliation: Department of Biomedical Sciences, Missouri State University, Springfield, MO 65897, USA. Electronic address: bentimson@missouristate.edu.
authors.forename: Benjamin F
authors.initials: BF
authors.lastname: Timson
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism* / Q000628:therapy*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D002540:Cerebral Cortex / Q000378:metabolism; D002950:Citrate (si)-Synthase / Q000378:metabolism; D004195:Disease Models, Animal; D005081:Exercise Therapy / Q000379:methods*; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D008822:Mice, Transgenic; D009043:Motor Activity; D018482:Muscle, Skeletal / Q000378:metabolism; D015260:Neprilysin / Q000378:metabolism; D010446:Peptide Fragments / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D011897:Random Allocation; D011973:Receptors, LDL / Q000378:metabolism; D016896:Treatment Outcome; D025521:Tumor Suppressor Proteins / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D016229:Amyloid beta-Peptides; D018840:HSP70 Heat-Shock Proteins; D026503:Low Density Lipoprotein Receptor-Related Protein-1; C486645:Lrp1 protein, mouse; D010446:Peptide Fragments; D012333:RNA, Messenger; D011973:Receptors, LDL; D025521:Tumor Suppressor Proteins; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42); D002950:Citrate (si)-Synthase; D015260:Neprilysin; D020780:Matrix Metalloproteinase 9; C501830:Mmp9 protein, mouse
keywords: Alzheimer's disease; Amyloid-β; Amyloid-β clearance proteins; Exercise training; Heat shock protein 70; Physical activity