qBead Assessment of miRNA in Alzheimer's Disease

描述(由申请人提供)：与阿尔茨海默病(AD)相关的miRNA生物标记物可能有助于诊断工具或在阐明疾病机制和发现新疗法方面有用，将使用一种新的全转录组QBead“X-MAP分析(尚未商业化推出)来识别。生物标志物将从脑部福尔马林固定(FFPE)组织和匹配的血清样本中识别，这些样本包括AD患者、诊断为帕金森氏病和痴呆(PD)的患者、神经病理诊断为血管性痴呆(VAD)的脑血管疾病患者和正常对照组(NC)。结果将使用匹配的冰冻组织以及qbead检测和聚合酶链式反应来验证。QBead X-MAP分析利用定量核酸酶保护分析(qNPA“)，同时测量miRNA和mRNA。它非常精确和灵敏。该计划将利用qBead分析来验证FFPE和血清在鉴定AD生物标志物方面的有效性，证实最近关于AD患者冰冻脑中miRNA水平改变的报道，并提供qBead全转录组miRNA分析应用的早期例子。在第二阶段，将包括信使核糖核酸生物标记物，研究将扩展到AD、PD、VAD和NC FFPE、血清、黄褐色涂层和血浆样本的更大训练集，以扩大生物标记物集，然后测试一组独立的样本以确认/验证生物标记物。 与公共卫生相关：阿尔茨海默病(AD)的miRNA生物标记物可用于诊断、确定疾病机制和作为药物发现的目标，将使用一种尚未商业化推出的基于全转录组qBead“X-map”的新分析方法从脑FFPE和血清中识别。qBead X-map分析利用定量核酸保护分析(qNPA“)，同时测量miRNA和mRNA。它非常精确和灵敏，将能够识别低丰度的miRNA和那些变化小到1.2倍的miRNA。这种微小的变化在组织中可能特别相关，在这些组织中，仅占样本40%的目标细胞群体的1.2倍变化可能反映这些细胞的50%变化。

DESCRIPTION (provided by applicant): miRNA biomarkers related to Alzheimer's disease (AD) that may be useful as a diagnostic tool or in elucidating the mechanisms of disease and discovery of novel therapeutics will be identified using a novel whole transcriptome qBead" X-MAP-based assay (not yet launched commercially). Biomarkers will be identified from brain formalin fixed (FFPE) tissue and matched serum samples of AD patients, patients diagnosed Parkinson's disease and dementia (PD), patients with cerebrovascular disease neuropathologically diagnosed as vascular dementia (VaD), and normal controls (NC). The results will be validated using matched frozen tissue and both the qBead assay and PCR. The qBead X-MAP assay utilizes the quantitative Nuclease Protection Assay (qNPA") and measures both miRNA and mRNA. It is very precise and sensitive. This program will exploit the qBead assay to validate the utility of FFPE and serum for identification of AD biomarkers, to confirm recent reports of altered miRNA levels in frozen brain of AD patients, and to provide an early example of an application of the qBead whole transcriptome miRNA assay. In Phase II mRNA biomarkers will be included and the studies expanded to a larger training set of AD, PD, VaD and NC FFPE, serum, buffy coat, and plasma samples to expand the biomarker set and then test an independent set of samples to confirm/validate the biomarkers. PUBLIC HEALTH RELEVANCE: miRNA biomarkers of Alzheimer's disease (AD) useful for diagnosis, for identifying mechanisms of disease, and as targets for drug discovery will be identified from brain FFPE and serum using a novel whole transcriptome qBead" X-MAP-based assay that has not yet been launched commercially. The qBead X-MAP assay utilizes the quantitative Nuclease Protection Assay (qNPA") and measures both miRNA and mRNA. It is very precise and sensitive and will enable the identification of low abundant miRNA and those that change by as little as 1.2-fold. Such small changes can be particularly relevant in tissues where a 1.2-fold change in a target population of cells making up only 40% of the sample may reflect a 50% change in those cells.