title: Chronic mild stress accelerates the onset and progression of the Alzheimer's disease phenotype in Tg2576 mice.
abstract: The etiology of the more common (sporadic) forms of Alzheimer's disease (AD) remains unknown, although age is the most important risk factor. Nevertheless, interactions between environmental risk factors and genetic background may also influence the onset and progression of sporadic AD. Chronic stress, associated with altered memory and other neurological processes, is thought to influence the pathogenesis of AD. Hence, we evaluated the effect of unpredictable and consecutive chronic mild stressors on the onset of an AD-related pathology in the Tg2576 mouse line that overexpresses the human amyloid-β protein precursor with the Swedish mutation (hAβPP(Swe)). Two months after exposure to chronic mild stress, 4 month-old animals that normally display no pathological features of AD, not only expressed pathological markers but also experienced cognitive dysfunction in the Morris water maze test. These findings suggest that chronic mild stress accelerates the onset of cognitive impairment and produces an increase in hippocampal amyloid-β and phospho-tau levels on a background of AD susceptibility.
authors: Division of Neurosciences, CIMA, University of Navarra, Pamplona, Spain. mcuadrado@unav.es
authors: Mar
authors: M
authors: Cuadrado-Tejedor
authors: Ana
authors: A
authors: Ricobaraza
authors: Diana
authors: D
authors: Frechilla
authors: Rafael
authors: R
authors: Franco
authors: Alberto
authors: A
authors: Pérez-Mediavilla
authors: Ana
authors: A
authors: Garcia-Osta
mesh_terms: D000367:Age Factors; D000544:Alzheimer Disease / Q000150:complications* / Q000235:genetics / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000818:Animals; D002908:Chronic Disease; D003072:Cognition Disorders / Q000209:etiology* / Q000235:genetics; D003345:Corticosterone / Q000097:blood; D004195:Disease Models, Animal; D018450:Disease Progression; D005260:Female; D006624:Hippocampus / Q000378:metabolism; D006801:Humans; D018782:Maze Learning; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation / Q000235:genetics; D010641:Phenotype; D010766:Phosphorylation / Q000235:genetics; D018709:Statistics, Nonparametric; D013315:Stress, Psychological / Q000097:blood / Q000150:complications* / Q000209:etiology*; D016875:tau Proteins / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D016875:tau Proteins; D003345:Corticosterone