中文摘要：

淀粉样蛋白级联假说是阐释阿尔茨海默病（Alzheimer＇s disease,AD）发病机制的主要学说之一,即脑内过量的β-淀粉样蛋白（β-amyloid,Aβ）是促发AD的核心因素.因此,靶向Aβ形成、聚集和清除等关键环节的药物开发是目前药物研究的热点.但近年来AD新药临床试验屡屡失败,至今尚未得到一种切实有效的治疗药物.淀粉样蛋白级联假说的局限性和痴呆期患者疾病进程的难以逆转,可能是临床试验反复失败的两个主要原因.借助AD早期诊断技术的发展,将药物干预的时间窗口前移,重视痴呆前期病理机制与治疗的研究,可能是研制延缓AD发生和发展有效药物的新途径.

英文摘要：

Alzheimer＇s disease （AD） is the most common cause of dementia among the elderly people. The prevailing hypothesis for the pathological progression of AD is the β-amyloid peptide （Aβ） cascade hypothesis： oligomeric forms of Aβ with cytotoxicity are the main cause of neuronal death in the brain of the AD patients. Thus, the inhibition of Aβ production and aggregation as well as improvement of its clearance appear to be the main strategy for drug development. However, the disturbing issue is that no significantly effective approach is available yet although a large number of compounds have been trialed on clinic. It questions the hypothesis that Aβ is the key pathologic factor leading to AD progression. The other possibility of failure is that loss of neural cells is so extensive that any treatment becomes not available when cognitive symptoms are apparent. New diagnostic ways may help to identify individuals before substantial neural damage has occurred. Treatments could then be attempted to stave off the onset of the disorders or the progression of the disease.