Optimization and Normalization Studies for Individual CSF Samples

描述（由申请人提供）： 阿尔茨海默病（AD）是痴呆症的最常见形式，并且是美国的第六大死亡原因。AD的最大已知风险因素是年龄增加;大多数AD患者年龄在65岁及以上。AD是一种进行性疾病，痴呆症状在几年内逐渐恶化。目前的AD治疗不能阻止疾病进展，但它们可以暂时减缓痴呆症状的进展，并改善AD患者及其护理人员的生活质量。目前还没有可用于预测AD发病的诊断性生物标志物，也没有可用于区分早期AD与年龄相关性痴呆的生物标志物。这样一个歧视性的工具将是非常宝贵的指导临床医生对早期干预的努力。细胞外RNA在生物流体中的存在代表了一种 可从中分离、表征和利用诊断和预后生物标志物的肥沃的分子景观。因此，在脑脊液（CSF）中的细胞外RNA的鉴定提供了一个机会，以确定重要的生物标志物，用于临床使用的特点痴呆症，如AD。MicroRNA是RNA的非蛋白质编码家族的成员，其充当转录后基因表达的调节剂。微RNA越来越多地在循环流体如CSF、血浆、血清和胎盘组织中被鉴定，其中它们的表达与包括脑损伤、退行性疾病和精神健康障碍在内的几种疾病相关。我们建议鉴定CSF中的microRNA，以检查它们作为AD诊断生物标志物的效用。为了实现这一目标，我们建立了一个高素质的多学科研究团队，拥有AD，痴呆和CSF生物标志物的专业知识，先进的基因组方法学，生物统计学和临床研究，以检查CSF中microRNA作为AD诊断生物标志物的临床效用。

DESCRIPTION (provided by applicant): Alzheimer's disease (AD) is the most common form of dementia and is the sixth leading cause of death in the United States. The greatest known risk factor for AD is increasing age; the majority of people with AD are age 65 and older. AD is a progressive disease, with dementia symptoms gradually worsening over several years. Current AD treatments cannot stop disease progression, but they can temporarily slow the progression of dementia symptoms and improve quality of life for those with AD and their caregivers. There is no diagnostic biomarker that can be used to predict the onset of AD, nor is there a biomarker which can distinguish early AD from age-related dementia. Such a discriminatory tool would be invaluable in guiding clinicians towards early interventional efforts. The existence of extracellular RNAs in biofluids represents a fertile molecular landscape from which diagnostic and prognostic biomarkers may be isolated, characterized, and exploited. Accordingly, the identification of extracellular RNAs in the cerebrospinal fluid (CSF) provides an opportunity to define important biomarkers for clinical use in characterizing dementias such as AD. MicroRNAs are members of the non-protein-coding family of RNAs that serve as regulators of post-transcriptional gene expression. MicroRNAs are increasingly being identified in circulating fluids such as CSF, plasma, serum, and placental tissue, where their expression is correlated with several diseases including brain injury, degenerative diseases, and mental health disorders. We propose to identify microRNAs in CSF to examine their utility as diagnostic biomarkers for AD. To achieve this goal, we have established a highly qualified, multidisciplinary investigative team with expertise AD, dementia, and CSF biomarkers, advanced genomic methodologies, biostatistics, and clinical studies to examine the clinical utility of microRNAs in CSF as diagnostic biomarkers for AD.