Biomarkers of Alzheimer's Disease

描述(申请人提供)：生物标记物是阿尔茨海默病(AD)早期准确诊断的迫切需要。SurroMed，Inc.正在使用高通量、代谢组和蛋白质组方法对人脑脊液(CSF)、血清和尿液中的数百到数千个分子进行差异化量化，以确定AD的生物标记物。低分子多肽和代谢物部分(代谢体)包含丰富多样的可能的AD生物标志物，但它从未被系统地研究过。我们建议开发方法来分离脑脊液、血清和尿液的代谢物，并利用微尺度液相色谱和质谱仪鉴定多肽和代谢物。这种基于发现的方法将与基于假设的方法相补充，在该方法中，我们使用免疫亲和捕获和/或MS来检查AD病理生理学中涉及的分子。因此，第一阶段将建立一个代谢组学平台，用于以前所未有的规模和高通量检测和鉴定AD生物标记物。这项技术将应用于随后的第二阶段应用，旨在通过对轻度认知障碍和阿尔茨海默病患者的临床研究，发现阿尔茨海默病早期阶段的生物标记物。

DESCRIPTION (provided by applicant): Biomarkers are urgently needed for the early and accurate diagnosis of Alzheimer's disease (AD). SurroMed, Inc. is using high throughput, metabolomic and proteomic approaches to differentially quantify hundreds to thousands of molecules in human cerebrospinal fluid (CSF), serum, and urine to identify biomarkers of AD. The low molecular peptide and metabolite fraction (the metabolome) contains a rich diversity of possible biomarkers of AD, yet it has never been systematically examined. We propose to develop methods to fractionate the metabolome of CSF, serum, and urine and identify peptides and metabolites using micro-scale liquid chromatography and mass spectrometry. This discovery-based approach will be complemented with a hypothesis-based approach in which we examine molecules implicated in AD pathophysiology using immuno-affinity capture and/or MS. Phase I will therefore establish a metabolomic platform for detection and identification of AD biomarkers at an unprecedented scale and with high throughput. This technology will be applied in a subsequent Phase II application aimed at discovering biomarkers for early stages of AD in a clinical study with mild cognitively impaired and AD patients.