由β淀粉样蛋白42原纤维诱导的P301l tau转基因小鼠中神经原纤维缠结的形成。

Formation of neurofibrillary tangles in P301l tau transgenic mice induced by Abeta 42 fibrils.

作者信息

Götz J, Chen F, van Dorpe J, Nitsch R M

机构信息

Division of Psychiatry Research, University of Zürich, August Forel Strasse 1, 8008 Zürich, Switzerland.

出版信息

Science. 2001 Aug 24;293(5534):1491-5. doi: 10.1126/science.1062097.

DOI:10.1126/science.1062097

PMID:11520988

Abstract

beta-Amyloid plaques and neurofibrillary tangles (NFTs) are the defining neuropathological hallmarks of Alzheimer's disease, but their pathophysiological relation is unclear. Injection of beta-amyloid Abeta42 fibrils into the brains of P301L mutant tau transgenic mice caused fivefold increases in the numbers of NFTs in cell bodies within the amygdala from where neurons project to the injection sites. Gallyas silver impregnation identified NFTs that contained tau phosphorylated at serine 212/threonine 214 and serine 422. NFTs were composed of twisted filaments and occurred in 6-month-old mice as early as 18 days after Abeta42 injections. Our data support the hypothesis that Abeta42 fibrils can accelerate NFT formation in vivo.

摘要

β-淀粉样蛋白斑块和神经原纤维缠结（NFTs）是阿尔茨海默病典型的神经病理学特征，但其病理生理关系尚不清楚。将β-淀粉样蛋白Aβ42纤维注射到P301L突变型tau转基因小鼠脑中，导致杏仁核内投射到注射部位的神经元细胞体中NFTs数量增加了五倍。加利亚斯银浸染法鉴定出含有在丝氨酸212/苏氨酸214和丝氨酸422位点磷酸化的tau蛋白的NFTs。NFTs由扭曲的细丝组成，早在Aβ42注射后18天就在6个月大的小鼠中出现。我们的数据支持Aβ42纤维可在体内加速NFT形成这一假说。