Department of Nuclear Medicine, Odense University Hospital, 5000 Odense C, Denmark.
Research Unit of Clinical Physiology and Nuclear Medicine, Department of Clinical Research, University of Southern Denmark, 5230 Odense M, Denmark.
Int J Mol Sci. 2024 Mar 31;25(7):3892. doi: 10.3390/ijms25073892.
The amyloid cascade hypothesis for Alzheimer's disease is still alive, although heavily challenged. Effective anti-amyloid immunotherapy would confirm the hypothesis' claim that the protein amyloid-beta is the cause of the disease. Two antibodies, aducanumab and lecanemab, have been approved by the U.S. Food and Drug Administration, while a third, donanemab, is under review. The main argument for the FDA approvals is a presumed therapy-induced removal of cerebral amyloid deposits. Lecanemab and donanemab are also thought to cause some statistical delay in the determination of cognitive decline. However, clinical efficacy that is less than with conventional treatment, selection of amyloid-positive trial patients with non-specific amyloid-PET imaging, and uncertain therapy-induced removal of cerebral amyloids in clinical trials cast doubt on this anti-Alzheimer's antibody therapy and hence on the amyloid hypothesis, calling for a more thorough investigation of the negative impact of this type of therapy on the brain.
阿尔茨海默病的淀粉样蛋白级联假说仍然存在，尽管受到了强烈质疑。有效的抗淀粉样蛋白免疫疗法将证实该假说的主张，即蛋白质淀粉样蛋白-β是疾病的原因。两种抗体，aducanumab 和 lecanemab，已被美国食品和药物管理局批准，而第三种，donanemab，正在审查中。FDA 批准的主要论点是假定治疗诱导了大脑淀粉样沉积的清除。lecanemab 和 donanemab 也被认为会导致认知能力下降的一些统计学上的延迟。然而，临床试验中常规治疗效果较差、非特异性淀粉样蛋白-PET 成像选择淀粉样阳性试验患者以及不确定的治疗诱导大脑淀粉样蛋白清除，对这种抗阿尔茨海默病抗体治疗以及淀粉样蛋白假说提出了质疑，呼吁对这种类型的治疗对大脑的负面影响进行更彻底的调查。
