Clinical Utility of MicroRNAs as Diagnostic Biomarkers of Alzheimer's Disease

描述(由申请人提供)： 阿尔茨海默病(AD)是最常见的痴呆症形式，是美国第六大主要死亡原因。已知的AD的最大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，痴呆症症状在几年内逐渐恶化。目前的AD治疗方法无法阻止疾病的发展，但它们可以暂时减缓痴呆症症状的进展，并提高AD患者及其照顾者的生活质量。目前还没有可以用来预测AD发病的诊断生物标志物，也没有可以区分早期AD和老年性痴呆的生物标志物。这种歧视性的工具在指导临床医生进行早期干预方面将是非常宝贵的。生物体液中细胞外RNA的存在代表了一种 肥沃的分子图景，从中可以分离、表征和利用诊断和预后生物标记物。因此，脑脊液(CSF)中细胞外RNA的鉴定为确定重要的生物标志物提供了机会，供临床用于确定痴呆的特征，如AD。MicroRNAs是非蛋白质编码的RNAs家族的成员，它是转录后基因表达的调节者。在脑脊液、血浆、血清和胎盘组织等循环液中越来越多地发现了microRNAs，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多种疾病有关。我们建议鉴定脑脊液中的microRNAs，以检验它们作为AD诊断生物标志物的作用。为了实现这一目标，我们建立了一支高素质的多学科研究团队，其专业知识包括AD、痴呆和脑脊液生物标记物、先进的基因组方法、生物统计学和临床研究，以检验脑脊液中microRNAs作为AD诊断生物标记物的临床应用。

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.