Oddo Salvatore, Vasilevko Vitaly, Caccamo Antonella, Kitazawa Masashi, Cribbs David H, LaFerla Frank M
Departments of Neurobiology and Behavior and Neurology, and Institute for Brain Aging and Dementia, University of California, Irvine, California 92697, USA.
J Biol Chem. 2006 Dec 22;281(51):39413-23. doi: 10.1074/jbc.M608485200. Epub 2006 Oct 20.
Increasing evidence points to soluble assemblies of aggregating proteins as a major mediator of neuronal and synaptic dysfunction. In Alzheimer disease (AD), soluble amyloid-beta (Abeta) appears to be a key factor in inducing synaptic and cognitive abnormalities. Here we report the novel finding that soluble tau also plays a role in the cognitive decline in the presence of concomitant Abeta pathology. We describe improved cognitive function following a reduction in both soluble Abeta and tau levels after active or passive immunization in advanced aged 3xTg-AD mice that contain both amyloid plaques and neurofibrillary tangles (NFTs). Notably, reducing soluble Abeta alone did not improve the cognitive phenotype in mice with plaques and NFTs. Our results show that Abeta immunotherapy reduces soluble tau and ameliorates behavioral deficit in old transgenic mice.
越来越多的证据表明，聚集蛋白的可溶性聚集体是神经元和突触功能障碍的主要介导因素。在阿尔茨海默病（AD）中，可溶性淀粉样β蛋白（Aβ）似乎是诱导突触和认知异常的关键因素。在此我们报告一项新发现，即在伴有Aβ病理的情况下，可溶性tau蛋白也在认知衰退中起作用。我们描述了在同时含有淀粉样斑块和神经原纤维缠结（NFTs）的老年3xTg-AD小鼠中，主动或被动免疫后可溶性Aβ和tau蛋白水平降低后认知功能得到改善。值得注意的是，仅降低可溶性Aβ并不能改善有斑块和NFTs的小鼠的认知表型。我们的结果表明，Aβ免疫疗法可降低可溶性tau蛋白水平，并改善老年转基因小鼠的行为缺陷。
