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

MicroRNA 作为阿尔茨海默病诊断生物标志物的临床应用

• 批准号: 8709012
• 负责人: JOSEPH F QUINN
• 金额: $ 31.99万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-08-01 至 2015-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8709012
• 关键词: Age; Alzheimer' s Disease; Bioinformatics; Biological Assay; Biological Markers; Biometry; Bipolar Disorder; Brain Diseases; Brain Injuries; Caregivers; Case-Control Studies; Cause of Death; Cerebrospinal Fluid; Clinical; Clinical Research; Code; Complex; Data Set; Degenerative Disorder; Dementia; Diagnosis; Diagnostic; Digestion; Disease; Disease Progression; Environment; Family; Gene Expression; Genes; Genomics; Goals; Human; Impaired cognition; Individual; Ischemia; Liquid substance; Living Donors; Magnetic Resonance Imaging; Medical; Memory Loss; Mental disorders; Methodology; MicroRNAs; Molecular; Multiple Sclerosis; Oregon; Participant; Patients; Performance; Pharmaceutical Preparations; Plasma; Prognostic Marker; Progressive Disease; Psyche structure; Qualifying; Quality of life; Ribonucleoproteins; Risk Factors; Role; Sampling; Societies; Staging; Symptoms; Testing; Tissues; Traumatic Brain Injury; United States; Variant; age related; brain cell; clinical Diagnosis; cohort; design; extracellular; human disease; improved; member; mild cognitive impairment; multidisciplinary; neuroimaging; nuclease; population based; pre-clinical; preclinical study; public health relevance; sex; tool

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.

描述（由申请人提供）： 阿尔茨海默病 (AD) 是最常见的痴呆症，也是美国第六大死因。 AD 已知的最大风险因素是年龄增长。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 治疗无法阻止疾病进展，但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 和年龄相关性痴呆的生物标志物。这种歧视性工具对于指导临床医生进行早期干预工作将具有无价的价值。生物体液中细胞外 RNA 的存在代表了 丰富的分子景观，可以从中分离、表征和利用诊断和预后生物标志物。因此，脑脊液 (CSF) 中细胞外 RNA 的鉴定提供了一个机会来定义重要的生物标志物，用于临床表征 AD 等痴呆症。 MicroRNA 是非蛋白质编码 RNA 家族的成员，充当转录后基因表达的调节因子。 MicroRNA 越来越多地在脑脊液、血浆、血清和胎盘组织等循环液中被发现，它们的表达与多种疾病相关，包括脑损伤、退行性疾病和精神健康障碍。我们建议鉴定脑脊液中的 microRNA，以检验它们作为 AD 诊断生物标志物的效用。为了实现这一目标，我们建立了一支高素质、多学科的研究团队，拥有 AD、痴呆和脑脊液生物标志物方面的专业知识、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 microRNA 作为 AD 诊断生物标志物的临床效用。