TRANSGENIC MODELS TO SUDY ALZHEIMERS DISEASE

产品描述阿尔茨海默病（AD）的临床特征是痴呆 和神经病理学上的淀粉样斑块，淀粉样血管病，营养不良 神经突、NFT、神经胶质增生以及神经元亚群和突触的丧失。 越来越多的证据表明，APP衍生的AB肽起着重要的作用。 在AD中的核心作用 该项目的目标是表征神经元 以及导致淀粉样蛋白生成和神经变性的神经胶质产物 并确定皮质AD相关的发病途径， 以治疗干预为目标。 表达PDGF启动子的小鼠 驱动的，选择性剪接的hAPP小基因，（PDGF-APP小鼠）开发了几种 AD神经病理学方面。 这一建议是利用这一点和相关的 研究脑淀粉样蛋白生成和淀粉样蛋白诱导的 在体内的神经退行性变，具有以下目的：1）确定 影响体内AB蛋白产生和B-淀粉样蛋白沉积的因素。（二） 确定PDGF-hAPP中是否发生神经元/突触变性 小鼠依赖于B-淀粉样蛋白的形成; 3）确定是否B-淀粉样蛋白在小鼠的B-淀粉样蛋白的形成。 脑导致神经元凋亡的异常诱导， 过程涉及兴奋性毒性机制。

DESCRIPTION Alzheimer's disease (AD) is characterized clinically by dementia and neuropathologically by amyloid plaques, amyloid angiopathy, dystrophic neurites, NFT's, gliosis, and loss of neuronal subpopulations and synapses. Increasing evidence suggests that the AB peptide derived from APP plays a central role in AD. The goals of this project are to characterize neuronal and glial products that contribute to amyloidogenesis and neurodegeneration and identify cortical AD-related pathogenetic pathways that could be targeted by therapeutic interventions. Mice expressing a PDGF-promoter driven, alternatively spliced hAPP minigene, (PDGF-APP mice) develop several aspects of AD neuropathology. This proposal is to utilize this and related models to study cerebral amyloidogenesis and amyloid-induced neurodegeneration in vivo with the following aims: 1) Determine what factors influence AB production and B-amyloid deposition in vivo.; 2) Determine whether development of neuronal/synaptic degeneration in PDGF-hAPP mice depends on B-amyloid formation; 3) Determine whether B-amyloid in the brain results in aberrant induction of neuronal apoptosis and whether this process involves excitotoxic mechanisms.