Amyloid-β antibody treatment leads to rapid normalization of plaque-induced neuritic alterations
Amyloid-β antibody treatment leads to rapid normalization of plaque-induced neuritic alterations
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DOI：
10.1523/jneurosci.23-34-10879.2003
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发表时间：
2003-11-26
影响因子：
5.3
通讯作者：
Hyman, BT
中科院分区：
文献类型：
--
作者：
Lombardo, JA;Stern, EA;Hyman, BT
淀粉样蛋白堆积成不溶性斑块是阿尔茨海默病的一个特征。神经元形态被斑块扭曲：它们不是本质上笔直的，而是比对照组织中的那些弯曲得多，它们的轨迹被改变，它们经常膨胀或肿胀，可能影响突触传递。通过淀粉样蛋白抗体清除斑块是治疗阿尔茨海默病的一种很有前途的治疗方法，通过一种未知的细胞机制导致痴呆症的稳定。斑块清除对斑块诱导的神经元改变的影响以前没有研究过。在这里，我们表明斑块和神经性病变在单剂量淀粉样蛋白抗体治疗后的极短时间内是可逆的。淀粉样蛋白清除和正常神经元几何形状的恢复早在单次治疗后4d观察到，并持续至少32 d。这些结果表明，一旦斑块被清除，神经元形态就会自我纠正，被动抗体治疗有可能逆转阿尔茨海默病引起的神经元损伤，从而直接影响认知能力下降。此外，神经营养不良的快速正常化表明成人神经系统具有意想不到的可塑性。
The accumulation of amyloid-beta into insoluble plaques is a characteristic feature of Alzheimer's disease. Neuronal morphology is distorted by plaques: rather than being essentially straight, they are substantially more curved than those in control tissue, their trajectories become altered, and they are frequently distended or swollen, presumably affecting synaptic transmission. Clearance of plaques by administration of antibodies to amyloid-beta is a promising therapeutic approach to the treatment of Alzheimer's disease, leading to stabilization of dementia by an unknown cellular mechanism. The effect of plaque clearance on plaque-induced neuronal alterations has not been studied previously. Here we show that both plaques and neuritic lesions are reversible in a strikingly short period of time after administration of a single dose of amyloid-beta antibody. Amyloid clearance and recovery of normal neuronal geometries were observed as early as 4d and lasted at least 32 d after a single treatment. These results demonstrate that, once plaques are cleared, neuronal morphology is self-correcting and that passive antibody treatment has the potential to reverse neuronal damage caused by Alzheimer's disease and, hence, directly impact cognitive decline. Moreover, the rapid normalization of neuritic dystrophy suggests an unexpected degree of plasticity in the adult nervous system.