β-淀粉样蛋白被动免疫治疗阿尔茨海默病的现状与策略

The situations and strategies of amyloid-β-directed passive immunotherapy for Alzheimer’s disease

β⁃淀粉样蛋白(Aβ)既是阿尔茨海默病发病机制中的重要病因,又是治疗的关键靶点之一。采取被动免疫途径清除脑组织Aβ是目前颇受临床关注的治疗策略。然而,各项临床试验至今尚未获得一致性的结论。对其研究现状的分析表明,Aβ被动免疫治疗失败的原因可能与Aβ⁃IgG免疫复合物所固有的糖基化修饰有关。因此,改良Aβ⁃IgG Fc片段N⁃糖基化修饰、采取促炎症反应⁃抗炎症反应序贯给药模式,可能是一种有效的被动免疫治疗策略。

It is widely believed that amyloidβ⁃protein(Aβ)plays a core role in the pathogenesis of Alzheimer's disease(AD).Thus Aβis one of main targets in the therapeutic explorations for AD.Currently,clearance of Aβby passive immunotherapy is an important strategy for the treatment of AD.However,no consistent conclusions have been obtained from various clinical trails.We summarize the current situations of Aβ⁃directed passive immunotherapy for AD,and speculate that the failure of Aβ⁃directed passive immunotherapy for AD may be related to the intrinsic characteristics of Aβ⁃IgG glycosylation.Therefore,modifications of N⁃glycosylation on the Fc domain of Aβ⁃IgG and using a sequential administration mode of proinflammation⁃antiinflammation may be an effective strategy for passive immunotherapy for AD.