Fluid biomarkers in primary tauopathies

原发性 tau 蛋白病中的液体生物标志物

• 批准号: 10648906
• 负责人: Chihiro Sato
• 金额: $ 23.33万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-08-01 至 2025-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10648906
• 关键词: Aliquot; Alzheimer disease detection; Alzheimer' s Disease; Alzheimer' s disease brain; Alzheimer' s disease risk; Alzheimer’s disease biomarker; Amyloid beta-Protein; Antibodies; Benchmarking; Binding; Biological Assay; Biological Markers; Blood; Blood Tests; Brain; Brain Pathology; Central Nervous System; Cerebrospinal Fluid; Clinic; Clinical Trials Design; Cohort Studies; Control Groups; Data; Development; Diagnosis; Digestion; Frontotemporal Lobar Degenerations; Goals; Human; Immunoprecipitation; Individual; Liquid substance; Mass Spectrum Analysis; Measures; Mental disorders; Methods; Microtubules; Molecular Profiling; Neurodegenerative Disorders; Pathologic; Pathology; Patients; Peptides; Pick Disease of the Brain; Plasma; Population; Preparation; Procedures; Progressive Supranuclear Palsy; Protein Isoforms; Qualifying; Research; Resources; Sampling; Sensitivity and Specificity; Site; Subgroup; Tauopathies; Testing; Tissue Sample; Translating; accurate diagnosis; biomarker performance; blood-based biomarker; brain tissue; candidate marker; cohort; comparison control; corticobasal degeneration; imaging biomarker; mutation carrier; nervous system disorder; novel; tau Proteins; tau-1

Project summary Over the past several years, blood-based biomarkers that accurately detect Alzheimer’s Disease (AD) brain pathology have been developed. However, there are no specific fluid or imaging biomarkers for primary tauopathies including progressive supranuclear palsy (PSP), corticobasal degeneration (CBD), and frontotemporal lobar degeneration (FTLD). We have recently identified specific species of tau in cerebrospinal fluid (CSF) that can identify subsets of primary tauopathies from healthy control groups and other tauopathies with moderate specificity and sensitivity. In this study, we propose to optimize mass spectrometry methods to better distinguish primary tauopathies in CSF. Based on the new methods, we will translate these primary tauopathy biomarkers to blood and test if they correlate with the biomarker measures in paired CSF. This study will provide first measures of primary tauopathies in blood and prepare for large cohort studies looking into primary tauopathy CSF and blood to distinguish subgroups of primary tauopathies or tauopathies from other neurological or psychiatric diseases. If blood biomarkers are developed, it will likely be widely used and could facilitate primary tauopathy research and diagnoses.

项目摘要 在过去的几年里，基于血液的生物标志物可以准确检测阿尔茨海默病（AD）大脑 病理学已经发展。然而，对于原发性高血压，没有特异性的液体或成像生物标志物。 tau蛋白病，包括进行性核上性麻痹（PSP）、皮质基底节变性（CBD）和 额颞叶变性（FTLD）。我们最近在脑脊髓中发现了特定种类的tau蛋白， 可以从健康对照组和其他tau蛋白病中识别原发性tau蛋白病子集的脑脊液（CSF） 具有中等特异性和敏感性。在这项研究中，我们建议优化质谱方法， 更好地区分CSF中的原发性tau蛋白病。基于新的方法，我们将翻译这些主要的 将tau蛋白病生物标志物与血液进行比较，并测试它们是否与配对CSF中的生物标志物测量相关。本研究 将提供血液中原发性tau蛋白病的第一个测量方法，并为研究 原发性tau蛋白病CSF和血液，以区分原发性tau蛋白病或tau蛋白病与其他tau蛋白病的亚组 神经或精神疾病。如果开发出血液生物标志物，它可能会被广泛使用， 促进原发性tau蛋白病的研究和诊断。