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阿尔茨海默病:从免疫疗法到免疫预防。

Alzheimer's disease: From immunotherapy to immunoprevention.

机构信息

Department of Cellular Neurology, Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany; German Center for Neurodegenerative Diseases (DZNE), 72076 Tübingen, Germany.

Department of Neurology and Emory National Primate Research Center, Emory University, Atlanta, GA 30322, USA.

出版信息

Cell. 2023 Sep 28;186(20):4260-4270. doi: 10.1016/j.cell.2023.08.021. Epub 2023 Sep 19.

Abstract

Recent Aβ-immunotherapy trials have yielded the first clear evidence that removing aggregated Aβ from the brains of symptomatic patients can slow the progression of Alzheimer's disease. The clinical benefit achieved in these trials has been modest, however, highlighting the need for both a deeper understanding of disease mechanisms and the importance of intervening early in the pathogenic cascade. An immunoprevention strategy for Alzheimer's disease is required that will integrate the findings from clinical trials with mechanistic insights from preclinical disease models to select promising antibodies, optimize the timing of intervention, identify early biomarkers, and mitigate potential side effects.

摘要

最近的 Aβ 免疫疗法试验首次提供了明确的证据,表明从有症状的患者大脑中清除聚集的 Aβ 可以减缓阿尔茨海默病的进展。然而,这些试验中取得的临床益处有限,这凸显了深入了解疾病机制的必要性,以及在发病级联过程中尽早干预的重要性。需要制定针对阿尔茨海默病的免疫预防策略,将临床试验的结果与临床前疾病模型的机制见解相结合,以选择有前途的抗体,优化干预时机,确定早期生物标志物,并减轻潜在的副作用。

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