Biomarkers of Alzheimer's Disease

描述（由申请人提供）：阿尔茨海默病（AD）的早期和准确诊断迫切需要生物标志物。surmed, Inc.正在使用高通量、代谢组学和蛋白质组学方法对人脑脊液（CSF）、血清和尿液中的数百至数千个分子进行差异量化，以识别AD的生物标志物。低分子肽和代谢物部分（代谢组）包含丰富多样的AD可能的生物标志物，但从未被系统地检测过。我们建议开发方法来分离脑脊液、血清和尿液的代谢组，并使用微尺度液相色谱和质谱法鉴定肽和代谢物。这种基于发现的方法将与基于假设的方法相辅相成，在这种方法中，我们使用免疫亲和捕获和/或ms来检查与AD病理生理相关的分子，因此，I期将建立一个代谢组学平台，以前所未有的规模和高通量检测和鉴定AD生物标志物。该技术将应用于随后的II期申请，旨在在轻度认知障碍和AD患者的临床研究中发现早期AD的生物标志物。

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.