Mixed Dementia Induced by Right Common Carotid Artery Occlusion in an Alzheimer Mouse Model

Abstract

Although vascular risk factors are associated with Alzheimer disease (AD), the effect of chronic cerebral hypoperfusion (CCH) on the progression of AD has not been widely evaluated. We aimed to evaluate whether CCH would aggravate the behavioral changes and plaque formation in an AD transgenic (Tg) mouse model. Female Tg2576 (Tg+) mice (an AD model) and their littermates (Tg-) were subjected to permanent right common carotid artery occlusion (rCCAO). The Morris water maze and object recognition tests were performed 6-8 weeks after the operation; the mice were then sacrificed. We evaluated cell death by histological studies and quantified the amount of amyloid plaques. An escape performance in the Morris water maze test was significantly impaired in Tg+ mice with or without rCCAO compared with that in Tg- mice, but this impairment was not different between Tg+ rCCAO- and sham-operated mice. Learning curve which was preserved in Tg+ sham-operated mice was impaired in Tg+ rCCAO-operated mice. On object recognition testing, Tg+ and Tg- mice with rCCAO showed a significant reduction in their discrimination ability compared with those without rCCAO but there was no difference in the discrimination ability between Tg+ and Tg- mice. On the histological examinations, there was no evident cellular death in the brains of experimental mice. The burden of amyloid plaques was not different between Tg+ rCCAO- and sham-operated mice. In conclusion, Tg+ rCCAO-operated mice had both cognitive deficits on spatial memory and non-spatial working memory induced in AD and VCI models, respectively. Moreover, an impairment of learning curve was synergistically induced from both pathomechanisms.