线粒体在阿尔茨海默病中的早期作用可能有助于解释当前β淀粉样蛋白假说的局限性

纽约(2010年10月13日)——在阿尔茨海默病患者出现记忆丧失之前，大脑神经元已经遭受了多年的伤害。哥伦比亚大学医学中心(Columbia University Medical Center)的研究人员在小鼠模型上进行的一项新研究发现，大脑的线粒体——细胞的动力来源——是这种疾病最早的受害者之一。这项发表在《美国国家科学院院刊》在线早期版上的研究还发现，受损的线粒体会损伤神经元突触，而神经元突触是正常大脑功能所必需的。“突触损伤是阿尔茨海默病最早的事件之一，但我们还不能找出导致损伤的事件，”该研究的首席研究员、哥伦比亚大学医学中心陶博阿尔茨海默病和衰老大脑研究所的临床病理学和细胞生物学教授、医学博士严石度说。“我们的新发现，以及之前的研究表明，线粒体的变化会损害突触，我们可能能够通过改善线粒体功能在早期阶段减缓阿尔茨海默氏症。”恢复线粒体功能的药物可能能够治疗阿尔茨海默病的早期阶段。一种潜在的药物，环孢素，已经用于器官移植和自身免疫性患者。Yan博士在之前的研究中发现，环孢素可以抑制免疫系统，但它也可以阻断β淀粉样蛋白(Aβ)肽诱导的线粒体损伤(Du et al。自然医学，2008)。然而，环孢素对其他患者长期使用有太多的毒副作用。 Dr. Yan is currently trying to alter the chemical structure of the drug to reduce its toxicity and to improve its ability to cross the blood brain barrier but preserve its protective effect on Aβ-mediated toxicity. Most Alzheimer's researchers initially believed that Aβ peptides caused the disease after aggregating together in large, extracellular plaques, a defining feature of Alzheimer's-affected brains. But Dr.Yan's findings, along with those of many other scientists, now point to an earlier role for Aβ peptides inside the brain's neurons. The mitochondria are damaged, the researchers found, when (Aβ) peptides breach the mitochondria's walls and accumulate on the inside. Even low concentrations of Aβ peptides, equivalent to the levels found in cells years before symptoms appear, impair the mitochondria, particularly mitochondria that supply power to the neuron's synapses. When filled with Aβ peptides, these synaptic mitochondria were unable to travel down the neurons' long axons to reach, and fuel, the synapse. And the mitochondria that did make the journey failed to provide adequate energy to operate the synapses. Without operating synapses, neurons are unable to function. "Since cyclosporin is already FDA approved for use in organ transplant and autoimmune patients, this research has the potential to lead to more rapid clinical trials and progress quickly," said Dr. Yan. Next, Dr. Yan and her team also plan to do more research on the role of tau, which like beta amyloid, is the protein associated most with the plaques and tangles seen at autopsy in the brains of those with Alzheimer's. This work was supported in part by the National Institute on Aging (NIA) of the National Institutes of Health (NIH), and the Alzheimer's Association. Authors of the paper are: Heng Du , Lan Guo, Shiqiang Yan, Alexander A. Sosunov, Guy M. McKhann, and Shirley ShiDu Yan. -####- The Taub Institute for Research on Alzheimer's Disease and the Aging Brain at Columbia University Medical Center is a multidisciplinary group that has forged links between researchers and clinicians to uncover the causes of Alzheimer's, Parkinson's and other age-related brain diseases and discover ways to prevent and cure these diseases. It has partnered with the Gertrude H. Sergievsky Center at Columbia University Medical Center which was established by an endowment in 1977 to focus on diseases of the nervous system. The Center integrates traditional epidemiology with genetic analysis and clinical investigation to explore all phases of diseases of the nervous system. For more information about these centers visit:http://www.cumc.columbia.edu/dept/taub/http://www.cumc.columbia.edu/dept/sergievsky/哥伦比亚大学医学中心在基础、临床前和临床研究、医学和健康科学教育以及患者护理方面处于国际领先地位。医学中心培养未来的领导者，包括许多内科医生、科学家、公共卫生专业人员、牙医和内科外科医生学院、梅尔曼公共卫生学院、牙科医学院、护理学院、艺术与科学研究生院生物医学部门以及联合研究中心和机构的护士。哥伦比亚大学内科和外科医生学院成立于1767年，是美国第一个授予医学博士学位的机构，也是美国最挑剔的医学院之一。哥伦比亚大学医学中心是纽约市和纽约州最大的医学研究企业所在地，也是美国最大的医学研究企业之一。如需更多信息，请访问www.cumc.columbia.edu．