Mechanism of Action of ABeta*56 in Alzheimer's Disease

描述(由申请人提供)：这项提案的广泛长期目标是了解阿尔茨海默病(AD)如何发生记忆丧失。我们最近已经证明，一种我们命名为A？*56的特定淀粉样β蛋白(AP)组件可能是AD小鼠模型Tg2576认知能力下降的原因。我们研究的直接目标是确认人脑中A56的存在。我们还将评估A56的存在相对于我们队列中存在的三组(正常、MCI和AD)的认知状态，以支持我们的假设，即A56扰乱了大脑的记忆功能。从长远来看，我们建议结合体外和体内的范例来破译Aü*56在Tg2576小鼠中的作用机制。最后，我们计划评估A56是否代表连接疾病的两个表型特征，即淀粉样斑块和神经原纤维缠结的A(实体。如果完成，这项提案可能会为治疗阿尔茨海默病提供新的方法，因为它的目标是专注于确定是什么导致记忆丧失，以及在阿尔茨海默病早期或阿尔茨海默病前期如何发生记忆丧失，在这一阶段，大脑的完整性仍然完好无损。

DESCRIPTION (provided by applicant): The broad long-term objective of this proposal is to understand how memory loss occurs in Alzheimer's disease (AD). We have recently shown that a specific amyloid beta (AP) assembly that we named A¿*56was likely the cause of cognitive decline in the mouse model of AD, Tg2576. The immediate objective of our research is to confirm the existence of A¿*56 in the human brain. We will also evaluate the presence of A¿*56 relative to the cognition status of the three groups (normal, MCI and AD) present in our cohort in order to support our hypothesis that A¿*56disrupts memory function in the brain. In a longer term, we propose to decipher the mechanism of action of A¿*56in Tg2576 mice combining in vitro and in vivo paradigms. Finally we plan to evaluate whether A¿*56represent the A(entity connecting the two phenotypic hallmarks of the disease, namely amyloid plaques and neurofibrillary tangles. If completed this proposal could provide novel approaches for treating Alzheimer's disease because its objective is focusing on identifying what causes memory loss and how memory loss occurs in early or pre- Alzheimer's disease, stage at which the integrity of the brain is still intact.