AGE-RELATED BIOMARKET CHANGES IN CEREBROSPINAL FLUID

脑脊液中与年龄相关的生物市场变化

• 批准号: 8958971
• 负责人: Suzanne Elizabeth Schindler
• 金额: $ 11.44万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-01 至 2017-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8958971
• 关键词: Adult; Affect; Age; Aging; Alzheimer' s Disease; Amyloid; Amyloid beta-Protein; Amyloid deposition; Award; Biological Markers; Brain Injuries; Brain Pathology; Cerebrospinal Fluid; Clinical; Clinical Trials; Cognitive; Cognitive aging; Collection; Data; Dementia; Diagnosis; Diagnostic; Diagnostic tests; Disease; Early Diagnosis; Early treatment; Elderly; Enrollment; Evaluation; Family health status; Foundations; Future; Hippocampus (Brain); Image; Impaired cognition; Individual; Injury; Liquid substance; Longevity; Magnetic Resonance Imaging; Measurement; Measures; Memory; Monitor; Neurodegenerative Disorders; Neuronal Injury; Neurons; Participant; Pathology; Patients; Peptides; Performance; Persons; Pharmaceutical Preparations; Phase; Population; Psychology; Radiology Specialty; Research; Resources; Risk; Sampling; Scientist; Societies; Statistical Methods; Testing; Time; Training; Universities; Variant; Washington; Work; age related; amyloid pathology; clinical care; cognitive performance; cognitive testing; cohort; design; improved; middle age; mild cognitive impairment; novel; outcome forecast; pre-clinical; predictive marker; prognostic; public health relevance; repository; statistics; tau Proteins

 DESCRIPTION (provided by applicant): Age-related longitudinal change in cerebrospinal fluid biomarkers of Alzheimer disease Alzheimer disease (AD) is the most common cause of dementia in older adults. AD-related brain pathology, which includes the accumulation and deposition of amyloid-ß peptide and tau protein, begins ~10- 20 years before the onset of dementia. Multiple failed drug trials for AD demonstrate that treatment late in the disease course, when patients have significant neuronal damage and dementia, is unlikely to be helpful. There is hope that treatment of early AD will be more effective. Significant efforts are underway to identify patients with "pre-clinical AD," those who have early AD-related brain pathology but are still cognitively normal, using fluid biomarkers or imaging tests. Leading fluid biomarkers for AD include low levels of amyloid-ß 42 (Aß42) and high levels of tau and phosphotau181 (ptau) in the cerebrospinal fluid (CSF). However, there is large person-to-person variation in levels of CSF Aß42, tau and ptau, and no clear cut-offs for diagnostic purposes. Measuring CSF biomarkers at multiple time points, then quantifying their rates of change, may correct for some of the individual variation in baseline CSF biomarker levels and provide a superior predictor of AD-related brain pathology. In this study, levels of CSF Aß40, Aß42, tau and ptau will be measured in individuals who have undergone two or more CSF collections. CSF biomarker trajectories will be plotted for individuals representing the entire adult lifespan (age 20-84). Th time course of CSF biomarker changes will be defined, including when CSF Aß42 levels begin to decline (consistent with amyloid deposition) and when CSF tau and ptau levels begin to increase (reflecting neuronal injury). Statistical methods will be used to determine whether the rate of change in biomarker levels, rather than single baseline measures, better predict neuronal injury, poor performance on cognitive tests, and progression to AD dementia. If the rate of change in biomarker levels, rather than baseline concentrations alone, better predicts AD dementia and related measures, this would impact efforts to identify individuals with pre-clinical AD for clinical trials and may affect clinical diagnostic testing for AD dementia.

 描述（由申请人提供）：阿尔茨海默病脑脊液生物标志物中与阿尔茨海默病相关的纵向变化阿尔茨海默病（AD）是老年人痴呆症的最常见原因。AD相关的脑病理学，包括淀粉样蛋白-β肽和tau蛋白的积累和沉积，在痴呆发作前约10- 20年开始。针对AD的多项失败的药物试验表明，当患者具有显著的神经元损伤和痴呆时，在疾病过程的后期进行治疗不太可能有帮助。早期AD的治疗有望更有效。正在进行重大努力，以确定患者与“临床前AD”，那些谁有早期AD相关的脑病理，但仍然认知正常，使用流体生物标志物或成像测试。领先的流体生物标志物， AD包括脑脊液（CSF）中低水平的淀粉样蛋白β 42（A β 42）和高水平的tau和磷酸化tau 181（ptau）。然而，CSF A β 42、tau和ptau的水平存在很大的人与人之间的差异，并且没有用于诊断目的的明确截止值。在多个时间点测量CSF生物标志物，然后量化其变化率，可以校正基线CSF生物标志物水平的一些个体差异，并提供AD相关脑病理学的上级预测因子。在本研究中，将在接受两次或多次CSF采集的个体中测量CSF A β 40、A β 42、tau和ptau的水平。将绘制代表整个成人寿命（20-84岁）的个体的CSF生物标志物轨迹。将定义CSF生物标志物变化的时间过程，包括CSF A β 42水平开始下降（与淀粉样蛋白沉积一致）的时间和CSF tau和ptau水平开始增加（反映神经元损伤）的时间。将使用统计方法来确定生物标志物水平的变化率，而不是单一基线测量，是否能更好地预测神经元损伤，认知测试表现不佳以及进展为AD痴呆。如果生物标志物水平的变化率，而不是单独的基线浓度，更好地预测AD痴呆和相关措施，这将影响识别临床前AD患者进行临床试验的努力，并可能影响AD痴呆的临床诊断测试。