Investigation Of The Expression And The Therapeutic Action Of CR1 And Clusterin In Cerebral Amyloid Angiopathy

Objective:Our study was aimed to investigate the role of clusterin protein in treating cerebral amyloid angiopathy.Method:Synthetic pep tide 113-122 of clusterin protein was infused into lateral ventricle of APP-PS1 transgenic mouse model (Tg6799) by using micro pump for 2 weeks. After 2 weeks infustion, we used water-maze experiment to evaluate cognitive function of transgenic mice. Enzyme-linked immunosorbent assay kit was used to measure the level of A?40 and A?42 of transgenic mouse's brain. Immunohistochemistry was used to evaluate the severity of cerebral amyloid angiopathy. Also, western-blot was used to measure the change of low density lipoprotein receptor-related protein 2 (LRP2) in order to investigate the possible mechanism of clusterin treatment.Result:After treatment of synthetic clusterin peptide 113-122 for 2 weeks, we found that memory dysfunction got improved in APP-PS1 transgenic mouse with comparison to control mouse. Consistently, the level of A?40 and A?42 decreased significantly in APP-PS1 transgenic mouse and the severity of cerebral amyloid angiopathy got improved in APP-PS1 transgenic mouse as well. The level of LRP2 was increased after synthetic clusterin peptide 113-122 treatment in APP-PS1 transgenic mouse, suggesting a possible role of LRP-2 in the mechanism of clusterin therapy in cerebral amyloid angiopathy.Conclusion:In this study, we found that clusterin peptide 113-122 treatment was able to decrease the level of A?40 and A?42, improve the severity of cerebral amyloid angiopathy and memory dysfunction of APP-PS1 transgenic mouse, through a mechanism involving LRP2 protein. These findings probably provided important evidence for future treatment of CAA.Objective:The aim of this study was to investigate the expression of CR1 in cerebral amyloid angiopathy (CAA).Method:APP-PS1 transgenic mouse (Tg6799) was used as animal model of CAA and B6/SJL mice were used as control. Mouse was euthanized and protein of hippocampus and surrounding brain tissue were extracted. Western-bolt and ELISA were used to measure the change of CR1 level in APP-PS1 transgenic mouse. Using CD31 and amyloid (3 as marker, we used immunoinfluenchemical staining to study the expression of CR1 in vessel of APP-PS1 transgenic mouse.Results:Western-bolt and ELISA study found that CR1 protein was significantly increased in APP-PS1 transgenic mouse in comparison to control mouse. Also, immunofluenchemisty study found that the expression of CR1 protein changed into "dot-like" shape in the endothelial layer of cerebral amyloid angiopahty of APP-PS1 transgenic mouse.Conclusion:CR1 plays an important role in the pathogenesis of cerebral amyloid angiopathy.