J Intern Med. 2014 Mar;275(3):296-303. doi: 10.1111/joim.12192.
Recent trials of anti-amyloid agents have not produced convincing improvements in clinical outcome in Alzheimer's disease; however, the reason for these poor or inconclusive results remains unclear. Recent genetic data continue to support the amyloid hypothesis of Alzheimer's disease with protective variants being found in the amyloid gene and both common low-risk and rare high-risk variants for disease being discovered in genes that are part of the amyloid response pathways. These data support the view that genetic variability in how the brain responds to amyloid deposition is a potential therapeutic target for the disease, and are consistent with the notion that anti-amyloid therapies should be initiated early in the disease process.
最近针对淀粉样蛋白的抗淀粉样蛋白药物的临床试验并未在阿尔茨海默病的临床结局方面产生令人信服的改善；然而，这些较差或不确定结果的原因仍不清楚。最近的遗传数据继续支持阿尔茨海默病的淀粉样蛋白假说，在淀粉样蛋白基因中发现了保护性变异体，并且在淀粉样蛋白反应途径的一部分基因中发现了常见的低风险和罕见的高风险疾病变异体。这些数据支持这样一种观点，即大脑对淀粉样蛋白沉积的反应的遗传变异性是该疾病的一个潜在治疗靶点，并且与抗淀粉样蛋白治疗应该在疾病过程的早期开始的观点一致。
