Biomarker Core

生物标记物核心摘要： 随着阿尔茨海默病(AD)分子诊断领域的日益重视，生物标记物的核心 有两个最重要的目标。首先，我们将在宾夕法尼亚大学延续一个非常成功的传统 储存和广泛分散临床核心获得的生物流体样本，同时对这些样本进行注释 具有允许在以下范围内进行淀粉样变性-Tau-神经变性(A/T/(N))分类的基线分子测量 NIA-AA框架。其次，我们将通过将公认的脑脊液和成像基础联系起来，铺平新的基础 A/T/(N)生物标记物对从新出现的基于血浆的生物标记物获得的测量和执行措施 这将有助于研究血管疾病对临床表型异质性的贡献。 这些目标将通过五个具体目标的活动来实现。目标1：监督和指导所有银行和 在ADRC UDS参与者中获得的生物流体样本的分散情况(目前n=537)。目标2：确定特征 已建立的生化标记物已在文献中报道，以注释所有临床核心 A/T/(N)分类方案内的样品。由(1)脑脊液定义的脑脊液生化标志物谱 淀粉样β1-42(脑脊液Aβ42)和(2)1-40(脑脊液Aβ40)，(3)脑脊液总tau(脑脊液t-tau)，(4)脑脊液tau 残基181处的磷酸化(脑脊液p-tau181)，(5)脑脊液神经细丝轻链(CSFNFL)，和(6)血浆NFL 将制定措施。目标3：将新出现的基于血浆的生物标记物与已建立的脑脊液和 成像生物标记物，以及神经病理学。我们将集中在血浆p-tau和血浆Aβ的检测上， 从死前获得的样本中验证措施是否与死后发现相一致。对于经过充分验证的化验， 我们将获得所有ADRC UDS参与者的血浆检测结果。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贡献。我们将支持 收集生物标志物指标(如：C反应蛋白、胆固醇、血红蛋白A1c、白介素6、同型半胱氨酸) 这使得能够评估所有ADRC UDS参与者的血管风险。目标5：提供建议和支持 宾夕法尼亚民主与发展中心内外的调查人员。

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.