Osinde M, Clavaguera F, May-Nass R, Tolnay M, Dev K K
Department of Neuroscience, Novartis Institutes for BioMedical Research, Novartis Pharma, Basel, Switzerland.
Neuropathol Appl Neurobiol. 2008 Oct;34(5):523-31. doi: 10.1111/j.1365-2990.2008.00936.x. Epub 2008 Feb 14.
In this study, we aimed to investigate the interaction between amyloid- and Tau-associated pathologies to gain further insights into the development of Alzheimer's disease. We examined the formation of neurofibrillary tangles (NFT) in adult mouse brain without the prior overexpression of Tau at embryonic or early post-natal stages to dissociate any developmental mechanisms.
Lentivirus technology was used to examine the effects of overexpressing mutant Tau-P301S in the adult mouse brains of both wild-type and amyloid precursor protein (APP)-transgenic mice.
We find that injection of lentivirus Tau-P301S into the hippocampus of adult wild-type mice increases levels of hyperphosphorylated Tau, as early as 3 months post injection. However, no NFT are found even after 13 months of Tau expression. In contrast, the overexpression of Tau-P301S in adult APP-transgenic animals results in the formation of Gallyas-stained NFT.
Our current findings are the first to show that overexpression of Tau-P301S in adult mice overexpressing APP, but not wild-type mice, leads to enhanced Tau-related pathology.
在本研究中，我们旨在探究淀粉样蛋白与tau相关病理之间的相互作用，以进一步深入了解阿尔茨海默病的发病机制。我们在成年小鼠大脑中检测神经原纤维缠结（NFT）的形成，且未在胚胎期或出生后早期预先过度表达tau，以分离任何发育机制。
利用慢病毒技术检测在野生型和淀粉样前体蛋白（APP）转基因成年小鼠大脑中过表达突变型tau-P301S的影响。
我们发现，将慢病毒tau-P301S注射到成年野生型小鼠的海马体中，早在注射后3个月就会增加过度磷酸化tau的水平。然而，即使在tau表达13个月后也未发现NFT。相比之下，在成年APP转基因动物中过表达tau-P301S会导致形成加利亚斯染色的NFT。
我们目前的研究结果首次表明，在过表达APP的成年小鼠而非野生型小鼠中过表达tau-P301S会导致tau相关病理增强。
