Although chronic stress is known to be linked with memory and other neurological 
disorders, little is known about the relationship between chronic stress and the 
onset or development of Alzheimer's disease (AD). In this study, we investigated 
the effects of long-term stress on the onset and severity of cognitive deficits 
and pathological changes in APPV717I-CT100 mice overexpressing human APP-CT100 
containing the London mutation (V717I) after exposure to immobilization stress. 
We found that chronic immobilization stress accelerated cognitive impairments, 
as accessed by the Passive avoidance and the Social Transfer of Food Preference 
(STFP) tests. Moreover, the numbers and densities of vascular and extracellular 
deposits containing amyloid beta peptide (Abeta) and carboxyl-terminal fragments 
of amyloid precursor protein (APP-CTFs), which are pathologic markers of AD, 
were significantly elevated in stressed animals, especially in the hippocampus. 
Moreover, stressed animals, also showed highly elevated levels of 
neurodegeneration and tau phosphorylation and increased intraneuronal Abeta and 
APP-CTFs immunoreactivities in the hippocampus and in the entorhinal and 
piriform cortex. This study provides the first evidence that chronic stress 
accelerates the onset and severity of cognitive deficits and that these are 
highly correlated with pathological changes, which thus indicates that chronic 
stress may be an important contributor to the onset and development of AD.