tRNA-derived RNA Fragments (tRF) as Prognostic and Diagnostic Biomarkers for Alzheimer’s Disease

tRNA 衍生的 RNA 片段 (tRF) 作为阿尔茨海默病的预后和诊断生物标志物

• 批准号: 10578546
• 负责人: Xiaoyong Bao
• 金额: $ 80万
• 依托单位: UNIVERSITY OF TEXAS MED BR GALVESTON
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-03-15 至 2026-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10578546
• 关键词: Address; Affect; Alzheimer disease prevention; Alzheimer disease screening; Alzheimer' s Disease; Alzheimer' s disease diagnosis; Alzheimer' s disease pathology; Alzheimer' s disease patient; Alzheimer' s disease therapeutic; Alzheimer’s disease biomarker; Amyloid; Amyotrophic Lateral Sclerosis; Anticodon; Bioinformatics; Biological; Biological Assay; Biological Markers; Biometry; Blood; Brain; Cerebrospinal Fluid; Clinical; Clinical Services; Cognitive; Data; Dementia; Development; Disease; Disease Progression; Evaluation; Family; Future; Genes; Goals; Hippocampus; Human; Individual; Lead; Longitudinal Studies; Machine Learning; Memory Disorders; Memory Loss; Methods; MicroRNAs; Modality; Monitor; National Institute on Aging; Nerve Degeneration; Neurodegenerative Disorders; Neuropsychology; Parents; Parkinson Disease; Patients; Peripheral; Persons; Phase; Plasma; Positron-Emission Tomography; Prevention; Process; Prognosis; Prognostic Marker; Publications; Qualifying; Quantitative Reverse Transcriptase PCR; RNA; Reporting; Research; Ribonucleases; Role; Sampling; Scanning; Screening procedure; Serum; Severity of illness; Small RNA; Testing; Tissues; Transfer RNA; Translational Research; Treatment Efficacy; Untranslated RNA; Visit; aged; angiogenin; biomarker panel; blood-based biomarker; brain magnetic resonance imaging; cognitive function; cognitive testing; diagnostic biomarker; diagnostic tool; differential expression; disease diagnosis; disease diagnostic; disorder prevention; endonuclease; epidemiology study; experience; feature selection; fluorodeoxyglucose positron emission tomography; follow-up; improved; insight; mild cognitive impairment; molecular marker; neuroimaging; nonalzheimer dementia; novel; novel diagnostics; pre-clinical; prognostic; progression marker; research clinical testing; skills; tau Proteins; tau-1; transcriptome sequencing

PROJECT SUMMARY/ABSTRACT tRNA-derived RNA Fragments (tRFs), a newly discovered family of non-coding RNAs (ncRNAs), are emerging as essential disease biomarkers and regulators. Our recent publication demonstrated that tRFs are the most impacted small ncRNAs (sncRNAs) by Alzheimer's disease (AD) in the hippocampus. The changes are mainly from five tRFs, with one proven to correlate with the disease severity of AD experimentally. The correlation between an AD-impacted tRF and AD severity was also present in serum samples , supporting tRFs as promising AD indicators and potential prognostic/diagnostic biomarkers. Herein, we propose exploring a combination of an unbiased discovery method and a newly developed biomedical quantification approach to investigate whether the expression level of tRFs in the peripheral serum reflects the onset and progress of AD. During the discovery R61 phase, we will determine the clinical reliability of serum biomarkers to differentiate AD subjects from healthy individuals or individuals with non-AD dementia or non-dementia neurodegenerative diseases (Aim 1). We will then determine the lead tRF signatures or signature compositions and investigate the correlation between their changes with AD severity (Aim 2). The studies of the R61 phase will be mainly cross-sectional. During the R33 phase, we will investigate whether the AD biomarkers and their quantification assay can distinguish AD from its early mild cognitive impairment (MCI) stage. We will determine biomarker changes in disease progression in patients between baseline and subsequent follow-up patient visits. The patients who are healthy or have stable MCI over the years will be used as controls. The culmination of these aims will benefit both prognosis and diagnosis of AD. The feasibility of this approach is established by sample availability and our extensive research experience in tRFs and clinical service experience in AD. The overall goal of our research is to discover AD molecular biomarkers that could improve AD prevention and diagnosis and monitor the therapeutic efficacy in the future.

项目总结/摘要 tRNA衍生的RNA片段（tRFs）是新近发现的一类非编码RNA（ncRNA） 作为重要的疾病生物标志物和调节剂。我们最近的出版物表明，tRFs是最 影响小ncRNA（sncRNA）的阿尔茨海默病（AD）在海马。变化主要是 从五个tRF，其中一个被证明与AD的疾病严重程度相关。的相关性 AD影响的tRF和AD严重程度之间的关系也存在于血清样本中，支持tRF是有希望的 AD指标和潜在的预后/诊断生物标志物。在此，我们建议探索一种 公正的发现方法和新开发的生物医学量化方法，以调查是否 外周血清中tRFs的表达水平反映了AD的发生和发展。在发现 R61阶段，我们将确定血清生物标志物的临床可靠性，以区分AD受试者和健康受试者。 个体或患有非AD痴呆或非痴呆神经变性疾病的个体（目的1）。我们将 然后确定导联tRF特征或特征成分，并研究它们之间的相关性， 随着AD严重程度的变化（目标2）。R61阶段的研究将主要是横向研究。在R33 我们将研究AD生物标志物及其定量分析是否能区分AD及其 早期轻度认知功能障碍（MCI）。我们将确定疾病进展中的生物标志物变化， 基线和后续随访患者访视之间的患者。健康或病情稳定的患者 将这些年的MCI用作对照。这些目标的实现将有利于预后， AD的诊断这种方法的可行性是建立在样本的可用性和我们广泛的研究 tRF经验和AD临床服务经验。我们研究的总体目标是发现AD 分子生物标志物，可以改善AD的预防和诊断，并监测治疗效果， 未来