Elucidating factors affecting blood levels of tau and GFAP in adults at risk for neurodegeneration

阐明影响有神经变性风险的成人血液中 tau 蛋白和 GFAP 水平的因素

• 批准号: 10711773
• 负责人: Christopher T. CAMPBELL
• 金额: $ 33.23万
• 依托单位: MESO SCALE DIAGNOSTICS, LLC
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-01-01 至 2024-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10711773
• 关键词: Adult; Advanced Development; Affect; Age; Algorithmic Analysis; Algorithms; Alzheimer disease screening; Alzheimer' s Disease; Alzheimer' s disease diagnostic; Alzheimer' s disease patient; Alzheimer' s disease related dementia; Alzheimer’s disease biomarker; Biological; Biological Assay; Biological Markers; Blood; Blood Tests; Clinical; Clinical Drug Development; Clinical Trials; Cognitive; Collaborations; Communities; Complex; Computerized Medical Record; Confidential Information; Data; Diagnosis; Diagnostic; Ethnic Origin; Evaluation; Gender; Genetic Diseases; Glial Fibrillary Acidic Protein; Goals; Government; Healthcare Systems; Impaired cognition; Individual; Kidney Failure; Linear Regressions; Link; Medical; Medical History; Medical Records; Methodology; Modeling; Morphologic artifacts; Motivation; National Institute on Aging; Nerve Degeneration; Neurologic; Normal Statistical Distribution; Patients; Persons; Pharmaceutical Preparations; Physiological Processes; Plasma; Population; Process; Prognosis; Protocols documentation; Research; Risk; Sampling; Specimen; Statistical Data Interpretation; Statistical Distributions; Test Result; Testing; Validation; Variant; age effect; biobank; diagnostic algorithm; early screening; ethnic diversity; individual patient; insight; large datasets; mathematical model; population based; pre-clinical; prognostic algorithm; prospective; tau Proteins; tool

In this supplemental project, we will gain insights into tau and GFAP as biomarkers for Alzheimer’s disease (AD) and related dementias (ADRDs) by leveraging ultrasensitive blood assays. Ultrasensitive blood tests are emerging as valuable tools to achieve several milestones set by the National Institute on Aging to advance urgently needed treatments for AD and ADRD. While multiple biomarkers show differences in median levels between AD patients versus controls, no single biomarker thus far can reliably diagnose or prognose individual patients. Clinical interpretation of individual tests remains complicated due to overlap between AD and non-AD groups. A biofluid signature for AD, which uses an algorithm to analyze data for multiple biomarkers, promises to significantly advance ultrasensitive blood tests as translatable biomarkers for diagnosis and prognosis. Here, a collaboration between Meso Scale Diagnostics, LLC. (MSD) and Kaiser Permanente will analyze specimens from the Kaiser- Permanente Research Biobank to study determinants and statistical distribution of tau and GFAP in a community-based population typical of the intended population for AD screening. These insights are critical to developing diagnostic algorithms for ethnically diverse, mixed- gender populations that span a large age range. In particular, we will determine complex cut- points for biomarkers influenced by age, gender, and ethnicity. We will develop and assess a mathematical model for biomarker distributions that can be incorporated into diagnostic and prognostic algorithms. Finally, we will explore root causes for unusually elevated plasma levels of tau and GFAP among individuals without cognitive complaints, which pose a significant challenge for interpreting biomarker concentrations.

在这个补充项目中，我们将深入了解 tau 和 GFAP 作为生物标志物 利用超敏感血液治疗阿尔茨海默病 (AD) 和相关痴呆症 (ADRD) 化验。超灵敏血液检测正在成为实现多个里程碑的宝贵工具 由国家老龄化研究所设立，旨在推进 AD 和 ADRD 的急需治疗。 虽然多种生物标志物显示 AD 患者与 AD 患者之间的中位水平存在差异。 对照，迄今为止没有任何一种生物标志物可以可靠地诊断或预测个体患者。 由于 AD 和 AD 之间的重叠，各个测试的临床解释仍然很复杂 非 AD 组。 AD 的生物流体特征，它使用算法来分析数据 多种生物标志物，有望显着推进超灵敏血液检测的可转化 用于诊断和预后的生物标志物。这里是 Meso Scale 之间的合作 诊断有限责任公司。 (MSD) 和 Kaiser Permanente 将分析来自 Kaiser- Permanente Research Biobank 将研究 tau 和 tau 的决定因素和统计分布 以社区为基础的人群中的 GFAP 是 AD 筛查的典型目标人群。 这些见解对于开发针对种族多样化、混合群体的诊断算法至关重要。 跨越较大年龄范围的性别人口。特别是，我们将确定复杂的切割 受年龄、性别和种族影响的生物标志物点。我们将开发并评估 生物标志物分布的数学模型，可纳入诊断和 预测算法。最后，我们将探讨血浆水平异常升高的根本原因 没有认知障碍的个体中 tau 蛋白和 GFAP 的含量，这构成了显着的 解释生物标志物浓度的挑战。