Alzheimer’s Disease Biomarker for Diagnosis and Prognosis

摘要 阿尔茨海默病（AD）是导致不可逆神经退行性变的痴呆症的最常见原因 和认知能力下降尽管广泛的努力和许多临床试验的潜在疾病修饰 目前还没有有效的方法来治疗或预防这种疾病。AD的核心病理特征 是聚集的Aβ42蛋白（淀粉样斑块）的细胞外沉积物和Aβ42蛋白的细胞内聚集物 过度磷酸化的tau蛋白（神经元缠结）。已经确定，神经元中的缺陷性自噬 细胞导致AD中的疾病病理学。自噬是一种生理过程， 参与长寿蛋白质和细胞器的基础周转的途径。几项研究 表明自噬在淀粉样蛋白从大脑中清除中起着重要作用， 自噬有助于AD脑中淀粉样蛋白聚集。现在人们普遍认为， 自噬活性先于Aβ42的积累和神经元损失。在这个项目中，我们将探索 AD中功能失调性自噬的新标记物的使用。

Abstract Alzheimer's disease (AD) is the most common cause of dementia leading to irreversible neurodegeneration and cognitive decline. Despite extensive efforts and numerous clinical trials of potential disease-modifying therapies, there is yet no effective way to cure or prevent this disease. The core pathological hallmarks of AD are extracellular deposits of the aggregated Aβ42 protein (amyloid plaques) and intracellular aggregates of hyper-phosphorylated tau (neurofibrillary tangles). It is well established that defective autophagy in neuronal cells contribute to disease pathology in AD. Autophagy is a physiological process and conserved degradation pathway which is involved in the basal turnover of long-lived proteins and organelles. Several studies demonstrated that autophagy plays an important role in amyloid clearance from the brain and that impaired autophagy contribute to amyloid aggregation in AD brains. It is well accepted now that deterioration of autophagy activity precedes the accumulation of Aβ42 and neuronal loss. In this project we will explore the usage of a new marker for dysfunctional autophagy in AD.