Neurodegenerative Disease Unit, Department of Basic Medicine, Neuroscience, and Sense Organs, University of Bari Aldo Moro, Bari, Italy.
Neurodegenerative Disease Unit, Department of Clinical Research in Neurology, University of Bari Aldo Moro, Cardinal G. Panico Pious Foundation, Tricase, Italy.
Ann Neurol. 2019 Mar;85(3):303-315. doi: 10.1002/ana.25410. Epub 2019 Jan 28.
The amyloid-β (Aβ) cascade hypothesis of Alzheimer disease (AD) holds that brain accumulation of Aβ initiates the disease process. Accordingly, drug research has targeted Aβ production, clearance, and deposition as therapeutic strategies. Unfortunately, candidate drugs have failed to show clinical benefit in established, early, or prodromal disease, or in those with high AD risk. Currently, monoclonal antibodies specifically directed against the most neurotoxic Aβ forms are undergoing large-scale trials to confirm initially encouraging results. However, recent findings on the normal physiology of Aβ suggest that accumulation may be compensatory rather than the pathological initiator. If this is true, alternative strategies will be needed to defeat this devastating disease. ANN NEUROL 2019;85:303-315.
阿尔茨海默病（AD）的淀粉样蛋白-β（Aβ）级联假说认为，大脑中 Aβ 的积累引发了疾病过程。因此，药物研究将 Aβ 的产生、清除和沉积作为治疗策略。不幸的是，候选药物在已确立的、早期或前驱期疾病或具有高 AD 风险的患者中未能显示出临床益处。目前，针对最具神经毒性的 Aβ 形式的单克隆抗体正在进行大规模试验，以确认最初令人鼓舞的结果。然而，最近关于 Aβ 正常生理学的发现表明，积累可能是代偿性的，而不是病理性的启动因素。如果这是真的，就需要采取替代策略来战胜这种毁灭性的疾病。神经病学年鉴 2019；85：303-315。
