title: The effect of ageing on neurogenesis and oxidative stress in the APP(swe)/PS1(deltaE9) mouse model of Alzheimer's disease.
abstract: Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterised by memory loss and impaired cognitive function. One of the hallmarks of AD is the formation of beta amyloid (Aβ) plaques. Aβ has neurodegenerative properties and aggregates in the brain, causing inflammation, oxidative stress and eventually neuronal loss. In AD, adult neurogenesis in the dentate gyrus (DG) of the hippocampus is known to be impaired. We tested how ageing affects neurogenesis and oxidative stress in the commonly used APP(SWE)/PS1(ΔE9) mouse model of AD and their wild type (wt) littermate controls aged 3, 5, 10 and 15months. Progenitor cell proliferation in the DG of APP/PS1 was lower at 3, 5 and 10months compared to controls, while oxidative stress in APP/PS1 mice was increased in the cortex at 3 and 5months of age compared to controls. The numbers of new neurons in the DG were decreased in APP/PS1 mice at 10 and 15months. In APP/PS1 mice, Aβ plaques were evident in the cortex from 3months onward; however these were small and few. Plaque size and number consistently increased with age in APP/PS1 mice. These results show that the damage to the brain occurs already very early in the brain, and although neurogenesis is impaired, it is still active even in late stage AD. Therefore, therapies would have the best effects if started early, but promoting neurogenesis may act in a protective and reconstructive way even in later stages of AD.
authors.affiliation: School of Biomedical Science, University of Ulster, Coleraine, Northern Ireland, UK.
authors.forename: Alison
authors.initials: A
authors.lastname: Hamilton
authors.forename: Christian
authors.initials: C
authors.lastname: Holscher
mesh_terms: D000375:Aging / Q000378:metabolism*; D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism; D000818:Animals; D049109:Cell Proliferation; D018891:Dentate Gyrus / Q000166:cytology / Q000378:metabolism* / Q000503:physiopathology; D004195:Disease Models, Animal; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism / Q000503:physiopathology; D051379:Mice; D055495:Neurogenesis / Q000502:physiology*; D009474:Neurons / Q000378:metabolism; D018384:Oxidative Stress / Q000502:physiology*; D053764:Presenilin-1 / Q000235:genetics / Q000378:metabolism
chemical_list: D016564:Amyloid beta-Protein Precursor; D053764:Presenilin-1