The genetic evidence implicating amyloid-β in the initial stage of Alzheimer's disease is unequivocal. However, the long biochemical and cellular prodromal phases of the disease suggest that dementia is the result of a series of molecular and cellular cascades whose nature and connections remain unknown. Therefore, it is unlikely that treatments directed at amyloid-β will have major clinical effects in the later stages of the disease. We discuss the two major candidate therapeutic targets to lower amyloid-β in a preventive mode, i.e., γ- and β-secretase; the rationale behind these two targets; and the current state of the field.

中文翻译：

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调节γ-和β-分泌酶作为阿尔茨海默病的早期预防

阿尔茨海默病初始阶段淀粉样蛋白 β 的遗传证据是明确的。然而，该疾病长期的生化和细胞前驱期表明痴呆是一系列分子和细胞级联反应的结果，其性质和联系仍然未知。因此，针对淀粉样蛋白 β 的治疗不太可能在疾病的后期产生重大的临床效果。我们讨论了以预防方式降低淀粉样蛋白 β 的两个主要候选治疗靶点，即 γ- 和 β- 分泌酶；这两个目标背后的基本原理；以及该领域的当前状态。