CLINICAL TRIAL: PHASE 3 MULTICENTER, RANDOMIZED, DOUBLE BLIND, PLACEBO CONTROLLE

这个子项目是许多利用 由NIH/NCRR资助的中心赠款提供的资源。子项目及 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 中心，但不一定是研究者所在的机构。 迄今为止，治疗AD的治疗选择集中在神经递质系统的修饰上，以最大限度地提高被疾病破坏的神经元回路中的剩余活性。 基于神经递质的方法可能为某些患者提供短暂的症状获益，但不能解决潜在的疾病过程或最终减缓疾病进展。AD神经退行性变的确切病因是目前神经科学研究的热点之一，特别是在家族性AD遗传连锁方面的最新进展，有力地表明β-淀粉样蛋白（A？）可能是病原体。 多个参数支持干预A？（1）所有已知的遗传连锁形式的AD直接影响A β的产生或沉积; (2)在AD中，A？清除似乎受损;和（3）AD被定义为通过A β沉积的淀粉样变性。在其他淀粉样蛋白生成疾病中，已经显示限制淀粉样蛋白的产生导致其清除并诱导临床改善。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The therapeutic options for treatment of AD have thus far focused on modifications of neurotransmitter systems to maximize the remaining activity in neuronal circuits ravaged by the disease. Neurotransmitter-based approaches may provide transient symptomatic benefit for some patients, but do not address the underlying disease process or, ultimately, slow disease progression. The precise cause of the neurodegeneration in AD is currently one of the most intensely investigated issues in neuroscience, and recent advances, in particular, in genetic linkage of familial AD, have strongly suggested that the beta-amyloid protein (A?) may be the causative agent. Multiple arguments support intervention in A? metabolism and/or clearance as a therapeutic approach to the treatment of AD: (1) All known genetically linked forms of AD directly affect either production or deposition of A?; (2) in AD, A? clearance appears to be impaired; and (3) AD is defined as an amyloidosis by the deposition of A?. In other amyloidogenic diseases, it has been shown that limiting production of the amyloid protein leads to its clearance and induces clinical improvement.