Biomarker Core

生物标志物核心

• 批准号: 10461088
• 负责人: ALICE S CHEN-PLOTKIN
• 金额: $ 24.49万
• 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/10461088
• 关键词: Aging; Alzheimer' s Disease; Alzheimer' s disease related dementia; Alzheimer’s disease biomarker; Amyloid; Amyloid beta-42; Amyloid beta-Protein; Area; Autopsy; Biochemical; Biological Assay; Biological Markers; Blood; Blood Vessels; Blood specimen; Cessation of life; Cholesterol; Classification; Classification Scheme; Clinical; 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; Nerve Degeneration; Participant; Pathology; Pennsylvania; Plasma; Positron-Emission Tomography; Process; Protocols documentation; Reporting; Research; Research Personnel; Risk; Sampling; Scheme; Site; Testing; Training Support; Translational Research; Universities; Vascular Diseases; Visit; assay development; base; biomarker validation; clinical heterogeneity; clinical phenotype; disorder risk; education research; feasibility testing; imaging biomarker; neurofilament; neuroimaging; neuropathology; peer; 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 有两个超现实的目标首先，我们将继续在宾夕法尼亚大学非常成功的传统， 将临床核心获得的生物液体样本进行储存和广泛分散，同时对这些样本进行注释 基线分子测量允许淀粉样-Tau-神经变性（A/T/（N））分类在 NIA-AA框架。第二，我们将通过将成熟的基于CSF和基于成像的 A/T/（N）生物标志物与从新兴的基于血浆的生物标志物获得的测量值之间的关系，并执行测量 这将允许研究血管疾病对临床表型异质性的贡献。 这些目标将通过沿着五个具体目标的活动来实现。目标1：监督和指导所有银行业务， 在ADRC UDS参与者（当前n=537）中获得的生物流体样本的分散。目标2：表征 文献中先前报告的已建立的生化生物标志物，以注释所有临床核心 A/T/（N）分类方案内的样本。CSF生化生物标志物特征定义为（1）CSF 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处磷酸化（CSF p-tau 181），（5）CSF神经丝轻链（CSF NfL），和（6）血浆NfL 将制定措施。目的3：将新出现的基于血浆的生物标志物与已建立的CSF相关， 成像生物标志物以及神经病理学。我们将专注于血浆p-tau和血浆Aβ的测定， 验证从死前获得的样本与死后发现的测量结果。对于经过充分验证的测定， 我们将获得所有ADRC UDS参与者的血浆测量结果。目标4：与其他核心协作， 研究血管疾病对临床表型异质性的影响。我们将支持 收集生物标志物指标（即CRP、胆固醇、血红蛋白A1 c、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：提供咨询和支持， 宾夕法尼亚州ADRC内外的调查人员。