Gureviciene Irina, Gurevicius Kestutis, Mugantseva Ekaterina, Kislin Mikhail, Khiroug Leonard, Tanila Heikki
A.I. Virtanen Institute, University of Eastern Finland, Kuopio, Finland.
Neuroscience Center, University of Helsinki, Helsinki, Finland.
J Alzheimers Dis. 2017;55(1):147-157. doi: 10.3233/JAD-160453.
Amyloid plaques, although inducing damage to the immediately surrounding neuropil, have been proposed to provide a relatively innocuous way to deposit toxic soluble amyloid-β (Aβ) species. Here we address this hypothesis by exploring spread and absorption of fluorescent Aβ to pre-existing amyloid plaques after local application in wild-type mice versus APP/PS1 transgenic mice with amyloid plaques. Local intracortical or intracerebroventricular injection of fluorescently-labeled Aβ in APP/PS1 mice with a high plaque density resulted in preferential accumulation of the peptide in amyloid plaques in both conventional postmortem histology and in live imaging using two-photon microscopy. These findings support the contention that amyloid plaques may act as buffers to protect neurons from the toxic effects of momentary high concentrations of soluble Aβ oligomers.
淀粉样斑块虽然会对紧邻的神经纤维网造成损伤，但有人提出它是一种相对无害的方式来沉积有毒的可溶性淀粉样β蛋白（Aβ）。在这里，我们通过在野生型小鼠与患有淀粉样斑块的APP/PS1转基因小鼠中局部应用荧光Aβ后，探索其向预先存在的淀粉样斑块的扩散和吸收情况，来验证这一假设。在斑块密度高的APP/PS1小鼠中进行局部皮质内或脑室内注射荧光标记的Aβ，无论是在传统的死后组织学检查还是使用双光子显微镜的活体成像中，该肽都优先在淀粉样斑块中积累。这些发现支持了淀粉样斑块可能起到缓冲作用，保护神经元免受瞬间高浓度可溶性Aβ寡聚体毒性影响的观点。
