Proteomic characterization of exosomes from AD patients

项目摘要/摘要 阿尔茨海默病(AD)的发病途径涉及β-淀粉样蛋白(A-β)- 含有由磷酸化的tau蛋白组成的斑块和神经原纤维缠结(NFT)。 只有对阿尔茨海默病进行临时性、对症治疗，才能有效改善疾病 干预是迫切需要的。阿尔茨海默病蛋白质信号的可用性可能会提高 临床试验设计和分析，增加成功药物开发的可能性 更好地理解和描述试验中的患者。中枢神经系统衍生的外切体可能是一种 代表疾病进展的蛋白质的来源。外切体的精确机制 AD的生产和贩运尚不清楚，尽管Rissman集团和其他人 证明了外切体作为生物标记物和预测治疗效果的实用性 在人类血浆中。在这项提案中，里斯曼博士和耶茨博士将利用这些独特的资源 提高对外切体内容和贩运的认识，促进AD领域的发展 诊断。

PROJECT SUMMARY/ABSTRACT The pathogenic pathways involved in Alzheimer's disease (AD) involve β-amyloid (Aβ)- containing plaques and neurofibrillary tangles (NFTs) composed of phosphorylated tau protein. With only temporary, symptomatic treatments for AD available, effective disease-modifying intervention is desperately needed. The availability of protein signatures of AD may improve clinical trial design and analysis, increasing the likelihood of successful drug development by a better understanding and characterization of patients in trials. CNS derived exosomes may be a source of proteins that signal the progress of the disease. The precise mechanisms of exosome production and trafficking in AD are not understood, although the Rissman group and others have demonstrated the utility of exosomes as biomarkers and for prediction of treatment effects in human plasma. In this proposal, Drs. Rissman and Yates will use these unique resources to advance the understanding of exosome contents and trafficking to advance the field of AD diagnosis.