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生物标志物可能作为诊断工具或阐明疾病机制和发现新疗法有用，将使用一种新的基于全转录组qBead x - map的检测方法（尚未商业化）进行鉴定。生物标志物将从AD患者、诊断为帕金森病和痴呆（PD）的患者、神经病理学诊断为血管性痴呆（VaD）的脑血管疾病患者和正常对照（NC）的脑福尔马林固定（FFPE）组织和匹配的血清样本中进行鉴定。结果将使用匹配的冷冻组织以及qBead测定和PCR进行验证。qBead X-MAP检测采用定量核酸酶保护检测（qNPA”），测量miRNA和mRNA。它非常精确和敏感。该项目将利用qBead测定法验证FFPE和血清在AD生物标志物鉴定中的应用，确认最近关于AD患者冷冻大脑中miRNA水平改变的报道，并提供qBead全转录组miRNA测定法应用的早期实例。在II期，mRNA生物标志物将被纳入研究范围，研究将扩展到一个更大的训练集，包括AD、PD、VaD和NC FFPE、血清、灰褐色被毛和血浆样本，以扩大生物标志物集，然后测试一组独立的样本来确认/验证生物标志物。

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.