早期综合干预有助延缓阿尔茨海默症的发生  

Early multidomain intervention to stave off Alzheimer's disease

作　　者：赫荣乔[1] 

机构地区：[1]中国科学院生物物理研究所,脑与认知科学国家重点实验室,北京100101

出　　处：《科学通报》2016年第32期3420-3427,共8页Chinese Science Bulletin

基　　金：国家重点基础研究发展计划(2012CB911000)资助

摘　　要：阿尔茨海默症(Alzheimer’s disease,AD)的典型病变包括认知异常、脑内amyloid?(A?)沉积形成的老年斑(senile plaque)、异常磷酸化Tau蛋白形成的神经纤维缠结(neurofibrillary tangles,NFTs)、胶质细胞激活以及脑萎缩.在近100多年的研究过程中,国内外同行把研究重点集中在AD的临床阶段,追求单一靶点的药物.然而,这些努力尚未在临床治疗上实现重大突破.当前,AD临床前阶段(preclinical phases)的早期病理变化和干预措施研究受到了相当的重视.为了延缓老年痴呆的发生,在强调多靶点药物研发的同时,其他干预方法,包括改善生活习惯、调节饮食、参与社会活动、进行适当的体育锻炼等,也在AD的防治中得以研究与应用.Alzheimer＇s disease is an irreversible, progressive brain disorder that slowly destroys memory and thinking skills, and eventually the ability to carry out the simplest tasks. In most people with Alzheimer＇s symptoms first appear in their mid-60s. The typical lesions of Alzheimer＇s disease （AD） feature in cognitive impairment, amyloid 13（A13） deposits （senile plaque）, hyperphosphorylation of Tan in neurofibrillary tangles （NTFs）, glial cells activation and cerebral atrophy. The plaques and tangles in the brain are considered to be the main features of Alzheimer＇s disease. Loss of connections between neurons in the brain deteriorates neuronal message transmission between different parts of the brain, and from the brain to muscles and organs in the body. Over one hundred years, a great deal of research has been focused on the dementia of clinical phase, and on single-target drugs to intervene the progression of AD. However, a real breakthrough in the treatment still needs to be made to stave off AD. Currently, to clarify early pathological changes of pre-clinical stage is imperative to understand AD. Although aging, family history and susceptibility genes have been considered to be the most important factors, the rapid increase of AD patients does not conform to Hardy-Weinberg equilibrium. Therefore, environmental factors are more important than genetic factors in AD. The onset of human metabolic disorders becomes more related and vulnerable to endogenous and exogenous environmental pathogenic factors than genetics. Different environmental factors had been found to disrupt the binding affinity of Tau to microtubules or DNA, and to diminish the stability of its cellular skeleton by inducing Tan phosphorylation and amyloid 13 deposition. For example, five year-old monkeys （Macaca mulatta） which were administrated with low concentrations of methanol for 2 years and suffered from senile plaque, AI3 deposits, neurofibrillary like-tangles in parietal lobe and hippocampus. However, the direct r

关 键 词：阿尔茨海默症 认知功能损害 老年斑 神经纤维缠结 多靶点干预 

分 类 号：R749.16[医药卫生—神经病学与精神病学]