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

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， 阿尔茨海默病（AD）和相关痴呆症（ADRD）通过利用超敏感血液 测定。超灵敏血液检测正在成为实现几个里程碑的有价值的工具 由国家老龄化研究所设立，以推进AD和ADRD急需的治疗。 虽然多种生物标志物显示AD患者与对照组之间的中位水平存在差异， 对照组中，迄今为止没有单一的生物标志物可以可靠地诊断或诊断个体患者。 由于AD和AD之间的重叠，个别测试的临床解释仍然复杂。 非AD组。AD的生物流体特征，其使用算法来分析数据， 多个生物标志物，有望显着推进超灵敏血液检测， 用于诊断和预后的生物标志物。在这里，Meso Scale Diagnostics，LLC. (MSD)凯撒医疗机构将分析来自凯撒的样本 Permanente Research Biobank研究tau蛋白的决定因素和统计分布， GFAP在AD筛查目标人群的典型社区人群中进行。 这些见解对于开发针对种族多样性、混合性和种族多样性的诊断算法至关重要。 年龄跨度很大的性别人群。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得分。我们将制定和评估一个 生物标志物分布的数学模型，可以结合到诊断和 预测算法最后，我们将探讨血浆水平异常升高的根本原因。 tau蛋白和GFAP在没有认知障碍的个体中的表达，这构成了一个重要的 解释生物标志物浓度的挑战。

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.