Chronic mild stress accelerates the onset and progression of the Alzheimer's disease phenotype in tg2576 mice
Keywords: 
Amyloid-β
cognitive impairment
GSK3β
stress
tau
Issue Date: 
Jan-2012
Publisher: 
Ios Press
ISBN: 
1387-2877
Citation: 
Cuadrado-Tejedor M, Ricobaraza A, Frechilla D, Franco R, Perez-Mediavilla A, Garcia-Osta A. Chronic mild stress accelerates the onset and progression of the Alzheimer's disease phenotype in Tg2576 mice. J Alzheimers Dis 2012;28(3):567-578.
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.

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