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： 随着阿尔茨海默氏病（AD）在分子诊断上的重点，生物标志物核心 有两个超大的目标。首先，我们将继续在宾夕法尼亚大学继续具有成功的传统 通过临床核心获得的银行业务和广泛分散的生物流体样品，同时注释这些样品 带有基线分子测量，可以在内部进行淀粉样蛋白 - tau-神经变性（a/t/（n））分类 NIA-AA框架。其次，我们将通过关联良好的CSF和基于成像的铺设新的基础 A/T/（N）生物标志物，从新兴等离子体的生物标志物获得的测量和进行测量 这将允许投资血管疾病对临床表型异质性的贡献。 这些目标将通过沿五个特定目标的活动实现。目标1：监督并指导所有银行业务和 在ADRC UDS参与者中获得的生物流体样品的分散（当前n = 537）。目标2：特征 先前在文献中报道的生物化学生物标志物已经注释所有临床核心 A/T/（N）分类方案中的样本。由（1）CSF定义的CSF生化生物标志物谱 淀粉样-BETA 1-42（CSFAβ42）和（2）1-40（CSFAβ40），（3）CSF总TAU（CSF T-TAU），（4）CSF TAU 在181（CSF P-TAU181），（5）CSF神经丝轻链（CSF NFL）和（6）血浆NFL 将建立措施。 AIM 3：将新兴的基于等离子体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。我们将专注于血浆P-TAU和等离子体Aβ的测定 验证来自针对事后发现的原子质的样品的衡量标准。用于验证的测定法， 我们将对所有ADRC UDS参与者获得血浆措施。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贡献。我们将支持 收集生物标志物测量的收集（即CRP，胆固醇，血红蛋白A1C，白介素6（IL-6），同型半胱氨酸） 这允许评估所有ADRC UDS参与者的血管风险。目标5：向 宾夕法尼亚州ADRC内外的调查人员。