脑衰老与阿尔茨海默病症状出现前阶段  

The Relationship Between Brain Aging and Preclinical Alzheimer′s Disease

作　　者：崔德华[1] 田小生[1] 王贺成[1] 王维[1] 肖卫忠[1] 樊东升[1] 

机构地区：[1]教育部和卫生部神经科学重点实验室,北京大学神经科学研究所,北京大学第三医院神经内科

出　　处：《生物化学与生物物理进展》2012年第8期741-746,共6页Progress In Biochemistry and Biophysics

基　　金：国家自然科学基金资助项目(30973145;81171015;81211140047);科技部重大课题项目(2012CB911000;2012CB911004);教育部博士点基金资助项目(20090001110058);国家基础科学人才培养基金;北医创新人才基金资助项目;中日合作老年神经退行疾病认知障碍的早期诊断国际合作项目(2012-2014)~~

摘　　要：脑衰老可分为生理性增龄变化与病理性变化,后者与阿尔茨海默病(Alzheimer's disease,AD)等神经退行性疾病的发生有关.生理性脑衰老与AD在发病早期具有相似的表现形式、病变特征、生化改变和发病机制.其共同的分子机制是异常蛋白质蓄积,提示两者有着相似的病理学基础,脑衰老可能是AD等神经退行性改变的最初级阶段,病理性脑衰老因素可能促进AD等神经退行性疾病的发生发展.临床前期AD(preclinical AD,PCAD)患者的脑、血液和脑脊液中可以检测到AD特定的生物标记物,但AD的临床症状并没有出现,因此也被称为"症状出现前AD(presymptomatic AD)".PCAD和对照组比较,氧化应激指标和高度不溶性Aβ42并没有显著性升高,寻找早期PCAD发病过程中新的可用于临床早期诊断的生物标记物、药物靶点将成为我们的关注重点.This article reviews the relationship between brain aging and Alzheimer＇s disease （AD）. Specific issues addressed include the question of whether AD and brain aging should be conceptually lumped or split, the extent to which AD and brain aging potentially share common molecular mechanisms, whether beta amyloid should be primarily considered a marker of AD or simply brain aging, and the definition of AD itself. A small percentage of individuals with normal antemortem psychometric scores meet the neuropathological criteria for AD termed ＂preelinical＂ AD （PCAD）. PCAD and control subjects were compared for oxidative stress markers, amyloid beta-peptide, and identification of protein expression differences, and observed a significant increase in highly insoluble monomeric Aβ42, but no significant differences in oligomeric Aβ nor in oxidative stress measurements between controls and PCAD subjects. Expression proteomics identified proteins whose trends in PCAD are indicative of cellular protection, possibly correlating with previous studies showing no cell loss in PCAD.

关 键 词：脑衰老 临床前期阿尔茨海默病 Β-淀粉样蛋白 磷酸化Tau 

分 类 号：R338[医药卫生—人体生理学] Q2[医药卫生—基础医学]