Immunotherapy for Alzheimer's disease (AD) is effective in improving cognitive function in transgenic mouse models of AD. Because the AN1792 [beta-amyloid (Aβ) 1-42] vaccine was halted because of T cell mediated ...Immunotherapy for Alzheimer's disease (AD) is effective in improving cognitive function in transgenic mouse models of AD. Because the AN1792 [beta-amyloid (Aβ) 1-42] vaccine was halted because of T cell mediated meningoencephalitis, many scientists are searching for a novel vaccine to avoid the T cell mediated immune response caused by the Aβ1-42. Importantly, the time when the immunization is begun can influence the immune effect. In this study, an adenovirus vaccine was constructed containing 10 × Aβ3-10 repeats and gene adjuvant CpG DNA. Transgenic AD mice were immunized intranasally for 3 months. After 10 × Aβ3-10 vaccine immunization, high titers of anti-Aβ42 IgG1 predominant antibodies were induced. In spatial learning ability and probe tests, the 10 × Aβ3-10 immunized mice showed significantly improved memories compared to control mice. The 10 × Aβ3-10 vaccine resulted in a robust Th2 dominant humoral immune response and reduced learning deficits in AD mice. In addition, the 10 × Aβ3-10 vaccine might be more efficient if administered before Aβ aggregation at an early stage in the AD mouse brain. Thus, the adenovirus vector encoding 10 × Aβ3-10 is a promising vaccine for AD.展开更多
The present study utilized beta amyloid (Aβ)-induced cell apoptosis in PC12 cells as a cell model of Alzheimer's disease to investigate the interaction between brain-derived neurotrophic factor (BDNF) and the tro...The present study utilized beta amyloid (Aβ)-induced cell apoptosis in PC12 cells as a cell model of Alzheimer's disease to investigate the interaction between brain-derived neurotrophic factor (BDNF) and the tropomyosin-related kinase B receptor. Results showed that Aβ(25-35) can reduce survival of PC12 cells and increase cleaved caspase-3 expression in PC12 cells. However, BDNF inhibited Aβ(25-35)-induced cytotoxicity and cleaved casapase-3 expression. Interestingly, pretreatment with the tropomyosin-related kinase receptor inhibitor K252a for 20 minutes prior to BDNF blocked the neuroprotective effect of BDNF on PC12 cells.展开更多
基金the National Natural Science Foundation of China, No. 30471927
文摘Immunotherapy for Alzheimer's disease (AD) is effective in improving cognitive function in transgenic mouse models of AD. Because the AN1792 [beta-amyloid (Aβ) 1-42] vaccine was halted because of T cell mediated meningoencephalitis, many scientists are searching for a novel vaccine to avoid the T cell mediated immune response caused by the Aβ1-42. Importantly, the time when the immunization is begun can influence the immune effect. In this study, an adenovirus vaccine was constructed containing 10 × Aβ3-10 repeats and gene adjuvant CpG DNA. Transgenic AD mice were immunized intranasally for 3 months. After 10 × Aβ3-10 vaccine immunization, high titers of anti-Aβ42 IgG1 predominant antibodies were induced. In spatial learning ability and probe tests, the 10 × Aβ3-10 immunized mice showed significantly improved memories compared to control mice. The 10 × Aβ3-10 vaccine resulted in a robust Th2 dominant humoral immune response and reduced learning deficits in AD mice. In addition, the 10 × Aβ3-10 vaccine might be more efficient if administered before Aβ aggregation at an early stage in the AD mouse brain. Thus, the adenovirus vector encoding 10 × Aβ3-10 is a promising vaccine for AD.
文摘The present study utilized beta amyloid (Aβ)-induced cell apoptosis in PC12 cells as a cell model of Alzheimer's disease to investigate the interaction between brain-derived neurotrophic factor (BDNF) and the tropomyosin-related kinase B receptor. Results showed that Aβ(25-35) can reduce survival of PC12 cells and increase cleaved caspase-3 expression in PC12 cells. However, BDNF inhibited Aβ(25-35)-induced cytotoxicity and cleaved casapase-3 expression. Interestingly, pretreatment with the tropomyosin-related kinase receptor inhibitor K252a for 20 minutes prior to BDNF blocked the neuroprotective effect of BDNF on PC12 cells.