Elucidating the measurement of telomeres: Development of a transdisciplinary, high-impact Telomere Research Network

项目摘要 这一多元化补充将支持劳伦W的职业发展。约韦伦 McLester-Davis是奥奈达部落的成员，也是唯一一位美国原住民研究生。 在杜兰大学考虑到获得博士学位和NIH的美国原住民人数很少， 在过去十年中提供的资金，早期有针对性的支持，特别是对特别合格的 美国原住民女性研究人员在STEM领域，是关键。该补充将支持 一个这样的候选人通过研究计划直接与她自己的职业目标， 阿尔茨海默氏症协会国际社会的主要专业兴趣领域 阿尔茨海默氏症的研究和治疗-特别是疾病检测， 生物标志物和多样性，以及与阿尔茨海默病相关的民族因素， 疾病（ADRD）。拟议补充与母公司U24（U24 AG 066528）一致， 建立了端粒研究网络（TRN），以确定最佳实践， 测量端粒长度（TL）适用于基于人群的研究，并确定 TL作为环境问题、心理社会压力和 疾病的易感性。拟议的补编将扩大 父母补助金与以下补充目标：目标1：确定关系 非裔美国人和土著人的TL与神经心理表现之间的关系 美国中年和老年人。据推测，国王的听觉语言 学习测试（RAVLT）和连线测试（TMT），它们捕捉了微妙的认知 与ADRD相关的变化将与外周血TL显着相关，范围内 非洲人和美洲原住民。目的2a：评估CSF中TL与 外周血假设在外周血中测量的TL与外周血中的TL显著相关。 与从从以下获得的白色血细胞（WBC）测量的TL相关： 脑脊液（CSF）。目的2b：评估TL与DNA甲基化的相关性- 基于年龄（DNAm年龄）从CSF中的细胞在中年和老年人。是 假设TL将与DNAm年龄相关，CSF TL将证明 CSF WBC与DNA年龄的相关性强于外周WBC中测量的TL。 这些目标的共同实现预计将有助于加强 少数民族儿童TL与神经心理学结果之间关系的理解 ADRD的人群和特定生物标志物。

PROJECT SUMMARY This diversity supplement will support the career development for Lauren W. Yowelunh McLester-Davis, a member of the Oneida tribe and the only Native American graduate student at Tulane University. Given the paucity of Native Americans receiving doctoral degrees and NIH funding over the last decade, early targeted support, particularly for exceptionally qualified female Native American researchers in STEMM fields, is critical. This supplement will support one such candidate through a research program directly aligned with her own career goals and key professional interest areas by the Alzheimer's Association International Society to Advance Alzheimer's Research and Treatment – specifically the relation between disease detection, biomarkers and diversity, and ethnoracial factors related to Alzheimer's disease and related disorders (ADRD). The proposed supplement is aligned with the parent U24 (U24AG066528), that established the Telomere Research Network (TRN) to determine best practices for measurement of telomere length (TL) applicable to population-based studies and determine the ability of TL to serve a sentinel of the environmental exposome, psychosocial stress, and disease susceptibility across the life course. The proposed supplement will expand the aims of the parent grant with the following supplemental AIMS: Aim 1: To determine the relationship between TL and neuropsychological performance in African American and Native American middle-aged and older adults. It is hypothesized that the Rey Auditory Verbal Learning Test (RAVLT) and the Trail Making Test (TMT), which capture subtle cognitive changes associated with ADRD, will be significantly associated with peripheral blood TL within African and Native Americans. Aim 2a: To assess the correlation between TL in CSF and peripheral blood. It is hypothesized that TL measured in peripheral blood with be significantly correlated with TL measured from TL measured from white blood cells (WBCs) obtained from cerebrospinal fluid (CSF). Aim 2b: To assess the correlation of TL with DNA methylation- based age (DNAm age) from cells in CSF in middle-aged and older adults. It is hypothesized that TL will be associated with DNAm age and that CSF TL will demonstrate a stronger correlation with DNAm age in CSF WBCs than TL measured in peripheral WBC. Together the achievement of these Aims is expected to contribute to an enhanced understanding of relation between TL and with neuropsychological outcomes in minoritized populations and specific biomarkers of ADRD.