阿尔茨海默病症状出现前阶段研究的战略意义

Research progress on preclinical Alzheimer＇s disease

阿尔茨海默病（Alzheimer’s Disease，AD）是一种神经退行性疾病，临床上以进行性记忆丢失和随之而来的痴呆为特点，而神经病理上则以老年斑、神经纤维缠结和突触丢失为特点。临床前期AD（preclinicalAD，PCAD）定义为能够在患者的脑和血液、脑脊液等检测到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、发现氧化应激指标和高度不溶性A842有显著性升高。AD研究应该着眼于PCAD和MCI时间窗及始动因素（initiator），紧密围绕导致神经元死亡的核心机制，研究PCAD的始动因素（基因、表观遗传、代谢关键酶、微量元素）、PCAD相关蛋白代谢的结构与功能基础以及PCAD相关蛋白相互作用与神经元功能紊乱之间的关系，阐明PCAD相关始动因素的特定改变导致AD相关蛋白结构与功能异常进而导致神经元功能紊乱、神经细胞死亡的机制，并在此基础上，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。这可以推动相关认知科学及神经科学研究的发展，减轻家庭和国家的经济负担，契舍国家十二五战略方针，具有重要的科学、经济和社会意义。

Alzheimer＇s disease （AD） is a neurodegenerative disorder characterized clinically by progressive memory loss and subsequent dementia and neuropathologically by senile plaques, neurofibrillary tangles, and synapse loss. A small percentage of individuals with normal antemortem psychometric scores meet the neuropathological criteria for AD termed ＇ preclinical＇ 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 Aβ342, but no significant differences in oligomeric Aβ nor in oxidative stress measurements between controls and PCAD subjects. Expression proteomies identified proteins whose trends in PCAD are indicative of cellular pro- tection, possibly correlating with previous studies showing no Cell loss in PCAD. This review summarizes information about the oxidative stress and Aβproteomics, diagnosis and clinical trials of PCAD, and further discusses the prospects of PCAD.