Biomarker Core

生物标志物核心

• 批准号: 10663884
• 负责人: ALICE S CHEN-PLOTKIN
• 金额: $ 24.57万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-08-15 至 2026-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10663884
• 关键词: Aging; Alzheimer' s Disease; Alzheimer' s disease related dementia; Alzheimer’s disease biomarker; Amyloid; Amyloid beta-Protein; Area; Autopsy; Biochemical; Biological Assay; Biological Markers; Blood; Blood Vessels; Blood specimen; Cessation of life; Cholesterol; Classification; Classification Scheme; Clinical; Collaborations; Collection; Communities; Consultations; Data; Dementia; Development; Doctor of Philosophy; Fostering; Genomics; Glycosylated hemoglobin A; Goals; Homocysteine; Image; Individual; Interleukin-6; Investigation; Ligands; Light; Literature; Magnetic Resonance Imaging; Measures; Molecular; Molecular Diagnosis; National Institute on Alcohol Abuse and Alcoholism; Nerve Degeneration; Normal Range; Participant; Pathology; Pennsylvania; Plasma; Positron-Emission Tomography; Process; Protocols documentation; Reporting; Research; Research Personnel; Risk; Sampling; Scheme; Site; Testing; Training; Translational Research; Universities; Vascular Diseases; Visit; assay development; biomarker validation; clinical heterogeneity; clinical phenotype; disorder risk; education research; feasibility testing; imaging biomarker; neurofilament; neuroimaging; neuropathology; peer; structural imaging; tau Proteins; tau-1; vascular contributions

BIOMARKER CORE SUMMARY: With the increasing emphasis in the Alzheimer’s Disease (AD) field on molecular diagnosis, the Biomarker Core has two over-arching goals. First, we will continue a highly-successful tradition at the University of Pennsylvania of banking and widely dispersing biofluid samples obtained by the Clinical Core, while annotating these samples with baseline molecular measures that allow for Amyloid-Tau-Neurodegeneration (A/T/(N)) classification within the NIA-AA framework. Second, we will pave new ground by relating well-established CSF- and imaging-based A/T/(N) biomarkers to measures obtained from emerging plasma-based biomarkers, and performing measures that will allow for investigation of the contribution of vascular disease to heterogeneity of clinical phenotype. These goals will be met through activities along five Specific Aims. AIM 1: Oversee and direct all banking and dispersal of biofluid samples obtained in ADRC UDS participants (current n=537). AIM 2: Characterize established biochemical biomarkers previously reported in the literature in order to annotate all Clinical Core samples within the A/T/(N) classification scheme. A CSF biochemical biomarker profile defined by (1) CSF amyloid-beta 1-42 (CSF Aβ42) and (2) 1-40 (CSF Aβ40), (3) CSF total tau (CSF t-tau), (4) CSF tau phosphorylated at residue 181 (CSF p-tau181), (5) CSF neurofilament light chain (CSF NfL), and (6) plasma NfL measures will be established. AIM 3: Relate emerging plasma-based biomarkers to established CSF and imaging biomarkers, as well as neuropathology. We will focus on assays of plasma p-tau and plasma Aβ, validating measures from samples obtained antemortem against postmortem findings. For well-validated assays, we will obtain plasma measures on all ADRC UDS participants. AIM 4: Collaborate with other Cores to investigate the contribution of vascular disease to heterogeneity of clinical phenotype. We will support the collection of biomarker measures (i.e. CRP, cholesterol, hemoglobin A1c, interleukin-6 (IL-6), homocysteine) that allow for assessment of vascular risk in all ADRC UDS participants. AIM 5: Provide advice and support to investigators within and outside the Penn ADRC.

生物标志物核心摘要： 随着阿尔茨海默病（AD）领域对分子诊断的日益重视，生物标志物核心 有两个总体目标。首先，我们将延续宾夕法尼亚大学非常成功的传统 存储和广泛分散由临床核心获得的生物流体样本，同时注释这些样本 基线分子测量可对淀粉样蛋白-Tau-神经变性 (A/T/(N)) 进行分类 NIA-AA 框架。其次，我们将通过将成熟的 CSF 和基于成像的方法联系起来，开辟新的领域。 A/T/(N) 生物标志物到从新兴血浆生物标志物获得的测量值，以及执行测量值 这将有助于研究血管疾病对临床表型异质性的影响。 这些目标将通过围绕五个具体目标开展的活动来实现。目标 1：监督和指导所有银行业务 ADRC UDS 参与者（当前 n=537）中获得的生物流体样本的分布。目标 2：表征 建立了先前在文献中报道的生化生物标志物，以便注释所有临床核心 A/T/(N) 分类方案内的样本。由 (1) CSF 定义的 CSF 生化生物标志物概况 淀粉样蛋白-β 1-42 (CSF Aβ42) 和 (2) 1-40 (CSF Aβ40)、(3) CSF 总 tau (CSF t-tau)、(4) CSF tau 在残基 181 (CSF p-tau181)、(5) CSF 神经丝轻链 (CSF NfL) 和 (6) 血浆 NfL 处磷酸化 将制定措施。目标 3：将新兴的基于血浆的生物标志物与已建立的 CSF 和 成像生物标志物以及神经病理学。我们将重点关注血浆 p-tau 和血浆 Aβ 的检测， 根据死后的结果验证死前获得的样本的测量结果。对于经过充分验证的检测， 我们将获得所有 ADRC UDS 参与者的血浆测量结果。目标 4：与其他核心合作 研究血管疾病对临床表型异质性的影响。我们将支持 收集生物标志物测量值（即 CRP、胆固醇、血红蛋白 A1c、白细胞介素 6 (IL-6)、同型半胱氨酸） 允许评估所有 ADRC UDS 参与者的血管风险。目标 5：提供建议和支持 宾夕法尼亚州 ADRC 内外的调查员。