Affiliations: [a] Division of Neurosciences, CIMA, University of Navarra, Pamplona, Spain | [b] Department of Anatomy, Faculty of Medicine, University of Navarra, Pamplona, Spain | [c] Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Navarra, Pamplona, Spain
Correspondence:
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Correspondence to: Mar Cuadrado-Tejedor, Division of Neurosciences, CIMA, University of Navarra, Avda. de Pío XII 55, 31008 Pamplona, Spain. Tel.: +34 948 194700; Fax: +34 948 194715; E-mail: [email protected].
Note: [1] Both authors contributed equally to this work.
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 (hAβPPSwe). 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.
Keywords: Amyloid-β, cognitive impairment, GSK3β, stress, tau
