It has been widely accepted that laminins are involved in pathogenesis of Alzheimer's disease (AD). Amyloid plaques in AD patients are associated with immunostaining using antibodies raised against laminin-111, and laminin-111 has been shown to prevent aggregation of amyloid peptides. Although numerous articles describe small peptides from laminin-111 that are capable to disaggregate amyloid buildups and reduce neurotoxicity in in vitro and in vivo models, there is no approved laminin-111-based therapeutic approaches for treatment of AD. Also, it has been shown that immunoreactivity to laminin-111 appears late in development of cerebral amyloidosis. Based on the published data, we hypothesize that aberrant interaction between amyloid-beta and α5-laminins such as laminin-511 prevents the necessary laminin signaling into neurons leading to neurodegeneration and contributing to the early development of AD. Laminin-511 is the key extracellular protein that protects neurons from anoikis, inhibits excitoxicity and provides signaling that stabilizes dendritic spines and synapses in the developed brain. Absence of the signaling from laminin-511 leads to behavioral defects in mice. Laminin-511 and hippocampal neurons are in direct contact and accumulation of amyloid-beta that has been shown to avidly bind laminin-511 may physically decouple the interaction between α5-laminins and the neuronal membrane receptors inhibiting the signaling. Under this hypothesis, protein domains and peptides from laminin α5 chain may have a therapeutic potential in treatment of AD and the appearance of laminin-111 in the amyloid plaques is simply a consequence of the disease.

中文翻译：

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淀粉样蛋白β和α5层粘连蛋白之间的异常相互作用可能是阿尔茨海默氏病中神经元功能障碍的驱动因素。

层粘连蛋白参与阿尔茨海默氏病（AD）的发病机理已被广泛接受。使用抗层粘连蛋白-111产生的抗体，AD患者的淀粉样蛋白斑与免疫染色相关，并且层粘连蛋白-111已被证明可防止淀粉样蛋白肽聚集。尽管有许多文章描述了层粘连蛋白111的小肽，它们能够在体外和体内模型中分解淀粉样蛋白堆积并降低神经毒性，但是尚无批准的基于层粘连蛋白111的治疗方法来治疗AD。而且，已经显示出对层粘连蛋白111的免疫反应性在脑淀粉样变性病发展的晚期出现。根据发布的数据，我们假设淀粉样蛋白-β和层粘连蛋白（如层粘连蛋白-511）之间的异常相互作用会阻止必要的层粘连蛋白信号传导至神经元，从而导致神经变性并促进AD的早期发展。层粘连蛋白511是重要的细胞外蛋白，可保护神经元免于失神经，抑制兴奋性毒性并提供稳定发达大脑中树突棘和突触的信号。层粘连蛋白511缺乏信号传导会导致小鼠行为缺陷。层粘连蛋白511和海马神经元直接接触，淀粉样β的积聚已被证明与层粘连蛋白511紧密结合，可能会物理上解耦α5层粘连蛋白与抑制信号传导的神经元膜受体之间的相互作用。在这个假设下，