Department of Neurology, Hope Center for Neurological Disorders, Knight Alzheimer's Disease Research Center, Washington University School of Medicine, St. Louis, Missouri, USA.
Ann Neurol. 2022 Jun;91(6):847-852. doi: 10.1002/ana.26351. Epub 2022 Mar 31.
APOE is the strongest genetic factor for late-onset Alzheimer's disease (AD). A specific conformation of the ApoE protein is present in amyloid-β (Aβ) containing plaques. Immunotherapy targeting ApoE in plaques reduces brain Aβ deposits in mice. Here, we evaluated the effects of the anti-human APOE antibody HAE-4 on amyloid plaques, Aβ-mediated tau seeding and spreading, and neuritic dystrophy in the 5XFAD amyloid mice expressing human ApoE4. HAE-4 reduced Aβ plaques as well as Aβ-driven tau seeding/spreading and neuritic dystrophy. These results demonstrate that HAE-4 may provide therapeutic effects on amyloid removal and Aβ driven downstream consequences such as tauopathy. ANN NEUROL 2022;91:847-852.
载脂蛋白 E（APOE）是晚发性阿尔茨海默病（AD）最强的遗传因素。载脂蛋白 E 蛋白的特定构象存在于含有淀粉样蛋白-β（Aβ）的斑块中。针对斑块中的 ApoE 进行免疫疗法可减少小鼠大脑中的 Aβ 沉积。在这里，我们评估了抗人 APOE 抗体 HAE-4 对 5XFAD 淀粉样蛋白小鼠中淀粉样斑块、Aβ 介导的 tau 播种和扩散以及神经原纤维缠结的影响，该小鼠表达人 ApoE4。HAE-4 减少了 Aβ 斑块以及 Aβ 驱动的 tau 播种/扩散和神经原纤维缠结。这些结果表明，HAE-4 可能对淀粉样清除和 Aβ 驱动的下游后果（如 tau 病）具有治疗作用。神经病学年鉴 2022；91：847-852。
