英国一些科学家在实验中发现一种抗体，可以阻止阿尔茨海默症发病的关键进程，为全新治疗方法铺路。研究人员在《神经科学期刊》（Journal of Neuroscience）发表论文，称这种抗体可以“关闭”蛋白质Dkk1，从而阻止淀粉样斑块在大脑中形成。
法新社3月6日援引论文内容报道，淀粉样斑块一旦形成，将导致大脑海马区中神经元的接触部位、即突触减少，从而破坏学习能力和记忆力。
论文作者、伦敦大学学院细胞和发展生物学学者帕特里夏·萨利纳斯说：“重要的是，这些研究成果为在阿尔茨海默症早期防止认知衰退带来希望。”（生物谷 bioon.com）
doi:10.1523/JNEUROSCI.4562-11.2012
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The Secreted Wnt Antagonist Dickkopf-1 Is Required for Amyloid β-Mediated Synaptic Loss
Silvia A. Purro, Ellen M. Dickins, Patricia C. Salinas
Extensive evidence supports a central role for amyloid-β (Aβ) in the pathogenesis of Alzheimer's disease (AD). Synaptic loss mediated by Aβ in early stages of the disease might contribute to cognitive impairments. However, little is known about the mechanism by which Aβ induces the loss of synapses. The expression of the Wnt antagonist Dickkopf-1 (Dkk1) is increased in brains of AD patients and in AD transgenic mouse models, suggesting that dysfunction of Wnt signaling could contribute to AD pathology. Here we report that acute exposure to Aβ oligomers induces Dkk1 expression together with the loss of synaptic sites. Importantly, Dkk1-neutralizing antibodies suppress Aβ-induced synapse loss in mouse brain slices. In mature rat hippocampal neurons, Dkk1 decreases the number of synapses without affecting cell viability. Ultrastructural analyses revealed that Wnt blockade decreases the size of presynaptic and postsynaptic terminals. Time-lapse recordings of RFP-labeled stable synaptic sites demonstrate that Dkk1 induces the dispersal of synaptic components. These findings identify Dkk1 as a potential therapeutic target for the treatment of AD.
