Department of Neurology, Xuan Wu Hospital of Capital Medical University, Beijing, China.
J Alzheimers Dis. 2014;38(2):437-44. doi: 10.3233/JAD-131124.
Mammalian target of rapamycin (mTOR) signaling has been suggested to be effective in modifying cognitive status in animal models of Alzheimer's disease (AD), but little is known about its role in AD patients. We hereby tested whether mTOR signaling was activated and whether activated mTOR signaling was related to the degree of cognitive deficits in patients with AD. Autopsy brain hippocampal tissues were obtained from controls and patients with AD and Western blots were performed using antibodies against mTOR signaling molecules and RagC, an upstream component of mTOR complex 1 (mTORC1) signaling. We found that expression of mTOR/p-mTOR and its downstream targets S6/p-S6 and Raptor/p-Raptor were expressed in the control and AD hippocampus. The expression levels of these signaling molecules were significantly increased in the hippocampus at the severe stages of AD, compared to controls and other stages of AD. Interestingly, Rictor expression level was unaltered. In addition, RagC was increased in the hippocampus at the early, moderate, and severe stages of AD. Our data indicate that mTORC1, but not mTORC2, was activated in the AD brains and that the level of mTOR signaling activation was correlated with cognitive severity of AD patients.
哺乳动物雷帕霉素靶蛋白（mTOR）信号已被证明可有效改善阿尔茨海默病（AD）动物模型的认知状态，但对于其在 AD 患者中的作用知之甚少。我们在此测试了 mTOR 信号是否被激活，以及激活的 mTOR 信号是否与 AD 患者认知缺陷的程度有关。从对照组和 AD 患者的尸检大脑海马组织中提取了组织，并使用针对 mTOR 信号分子和 RagC（mTORC1 信号的上游成分）的抗体进行了 Western blot 分析。我们发现 mTOR/p-mTOR 及其下游靶标 S6/p-S6 和 Raptor/p-Raptor 在对照组和 AD 海马体中均有表达。与对照组和 AD 的其他阶段相比，AD 严重阶段的海马体中这些信号分子的表达水平显著增加。有趣的是，Rictor 的表达水平没有改变。此外，在 AD 的早期、中期和晚期，RagC 在海马体中增加。我们的数据表明，mTORC1 而不是 mTORC2 在 AD 脑中被激活，并且 mTOR 信号激活的水平与 AD 患者认知严重程度相关。
