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

项目摘要/摘要 TRNA衍生的RNA片段(TRFs)是一个新发现的非编码RNA(NcRNAs)家族 作为基础疾病的生物标志物和监管者。我们最近的出版物表明，TRF是最 阿尔茨海默病(AD)影响海马区的小ncRNAs(SNcRNAs)。变化主要是 来自五个TRF，其中一个被实验证明与AD的疾病严重程度相关。这种关联性 血清样本中也存在受AD影响的TRF和AD严重程度之间的关系，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，我们建议探索一种组合 无偏见的发现方法和新开发的生物医学量化方法 外周血中TRFs的表达水平反映了AD的发生发展。在发现的过程中 R61阶段，我们将确定血清生物标记物区分AD患者和健康患者的临床可靠性 个人或患有非痴呆性痴呆或非痴呆性神经退行性疾病的个人(目标1)。我们会 然后确定主要的TRF签名或签名成分，并调查它们之间的相关性 随着AD严重性的变化(目标2)。对R61相的研究将主要是横截面的。在R33期间 阶段，我们将调查AD生物标志物及其定量检测是否可以区分AD和其 早期轻度认知障碍(MCI)阶段。我们将确定生物标记物在疾病进展中的变化 患者在基线和随后的后续患者就诊之间。身体健康或病情稳定的患者 多年来的MCI将被用作对照。这些目标的最终实现将有利于预后和 诊断阿尔茨海默病。这种方法的可行性是通过样本的可获得性和我们的广泛研究来确定的 有TRF经验和AD临床服务经验。我们研究的总体目标是发现AD 可提高AD预防和诊断及监测疗效的分子生物标志物 未来。

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.