Plasma Phosphorylated-Tau, Neurodegeneration, and Clinical Outcomes-Childcare Supplement

血浆磷酸化 Tau、神经变性和临床结果 - 儿童保育补充剂

基本信息

批准号：
10845204
负责人：
Corey Bolton
金额：
$ 0.25万
依托单位：
VANDERBILT UNIVERSITY MEDICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-09-01 至 2023-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10845204
关键词：
Acceleration Activities of Daily Living Affect Age Aging Alzheimer disease screening Alzheimer&apos s Disease Alzheimer&apos s disease pathology Alzheimer’s disease biomarker Amyloid beta-Protein Atrophic Autopsy Biological Markers Biometry Blood Brain Caring Cerebrospinal Fluid Child Care Clinic Clinical Clinical Management Clinical Research Clinical Trials Cognition Cognitive aging Collaborations Data Data Collection Dementia Deposition Development Diagnostic Specificity Disease Disease Progression Elderly Enzyme-Linked Immunosorbent Assay Episodic memory Epitopes Etiology Failure Future Impaired cognition Inferior Institution International Knowledge Laboratories Letters Liquid substance Literature Longitudinal cohort study Magnetic Resonance Imaging Measurement Measures Medial Memory Mentors Mentorship Methods Nerve Degeneration Neuropsychology Observation in research Observational Study Outcome Outcomes Research Pathologic Patient Care Pattern Phosphorylation Plasma Population Positioning Attribute Positron-Emission Tomography Predictive Value Prevention Prognosis Proteins Protocols documentation Public Health Questionnaires Reporting Research Research Personnel Resources Scientist Sensitivity and Specificity Site Specificity Spinal Puncture Statistical Data Interpretation Stroke Structure Sweden Techniques Technology Temporal Lobe Thick Thinness Threonine Training Training Activity Universities University Hospitals Venous abeta accumulation abnormally phosphorylated tau angular gyrus biomarker development biomarker validation brain dysfunction brain magnetic resonance imaging career clinical care clinical trial enrollment clinically relevant cohort dementia care effective therapy executive function experience follow-up global health imaging science informant innovation insight instrumental activity of daily living multi-atlas segmentation neurochemistry neuroimaging novel marker potential biomarker regional atrophy screening single molecule skills specific biomarkers tau Proteins tau-1 tool

项目摘要

PROJECT SUMMARY Dementia due to Alzheimer’s disease is a global health crisis that is intensified by the absence of disease modifying treatments. The failure of past clinical trials in Alzheimer’s disease has been due in part to late initiation of treatment and inaccurate screening for study inclusion. In clinical settings, there are numerous causes of cognitive decline in aging and treatment and prognosis vary depending on the underlying etiology. Current methods of screening for Alzheimer’s pathology include cerebrospinal fluid analysis and positron emission tomography, both of which are not widely accessible. For both the research lab and the clinic, development of an accessible and accurate early marker of Alzheimer’s pathology is essential. Recent technological advances in highly sensitive single-molecule array techniques have created the opportunity to accurately measure phosphorylated tau (p-tau), a pathological hallmark of Alzheimer’s disease, in the blood. Plasma p-tau has emerged as a leading blood-based Alzheimer’s biomarker, showing strong correlations with other markers of Alzheimer’s pathology, distinguishing clinical Alzheimer’s disease from other dementia subtypes, and accurately predicting post-mortem Alzheimer’s pathology. Plasma p-tau has shown tremendous potential, yet existing research has largely focused on establishing the sensitivity and specificity of this biomarker for Alzheimer’s disease; its ability to predict more clinically meaningful longitudinal outcomes remains in question. The proposed research will examine baseline plasma p-tau in a longitudinal cohort study of aging as it relates to longitudinal neurodegeneration and clinical outcomes over a 9-year follow-up period. Highly clinically relevant outcomes were selected, including neurodegeneration, domain-based cognition, subjective cognitive decline, and functional abilities for activities of daily living, to maximize the potential of this biomarker being meaningfully integrated into clinical care. The proposed research will leverage the rich resources of the Vanderbilt Memory & Alzheimer’s Center, Vanderbilt University Institute of Imaging Science, and the Clinical Neurochemistry Laboratory of Sahlgrenska University Hospital, Sweden. The research will be guided by an interdisciplinary mentorship team, including experts in geriatric neuropsychology, Alzheimer’s disease, magnetic resonance imaging, subjective cognitive decline, fluid biomarkers, clinical management of abnormal cognitive aging, and statistical analysis. The parallel training plan will facilitate the candidate’s acquisition of the necessary knowledge and skills to study blood-based Alzheimer’s biomarkers and propel him into a successful career as an independent clinician-scientist. Understanding the predictive validity of plasma p-tau for clinically relevant outcomes would provide essential information that is necessary for the further development of this biomarker as a tool for clinical trial enrollment, accurate observational research in Alzheimer’s disease, and clinical care of dementia.

项目摘要由于阿尔茨海默氏病而引起的痴呆是一种全球健康危机，受疾病缺乏的启发修改治疗。过去在阿尔茨海默氏病中临床试验的失败部分是由于迟到在临床环境中，有很多衰老和治疗以及预后的认知能力下降的原因因潜在病因而异。当前的阿尔茨海默氏病筛查方法包括脑脊液分析和正电子排放断层扫描，两者都无法广泛访问。对于研究实验室和诊所，必须开发阿尔茨海默氏病理学的可访问且准确的早期标记。最近的高度敏感的单分子阵列技术的技术进步已经创造了机会精确测量了血液中阿尔茨海默氏病的病理标志的磷酸化tau（p-tau）。血浆P-TAU已成为主要的血液基于血液的生物标志物，显示出与阿尔茨海默病理学的其他标记，将阿尔茨海默氏病与其他痴呆症区分开亚型，并准确预测验尸后阿尔茨海默氏病的病理。等离子体p-tau显示出巨大的潜力，但现有的研究主要集中于建立这种敏感性和特异性阿尔茨海默氏病的生物标志物；它可以预测更有意义的纵向结局的能力仍然有问题。拟议的研究将在纵向队列研究中检查基线等离子体P-TAU 与纵向神经变性和临床结局有关的衰老，在9年的随访期内。选择了高度临床相关的结果，包括神经变性，基于域的认知，主观认知能力下降和日常生活活动的功能能力，以最大程度地发挥这种潜力生物标志物被有意义地整合到临床护理中。拟议的研究将利用富人范德比尔特记忆与阿尔茨海默氏症中心的资源，范德比尔特大学成像科学研究所，以及瑞典Sahlgrenska大学医院的临床神经化学实验室。研究将是在跨学科心态团队的指导下，包括老年神经心理学专家，阿尔茨海默氏症疾病，磁共振成像，主观认知下降，流体生物标志物，临床管理异常认知衰老和统计分析。并行培训计划将促进候选人的获取必要的知识和技能来研究基于血液的阿尔茨海默氏症并推动他成为独立临床科学家的成功职业。了解血浆的预测有效性 P-TAU用于临床相关的结果将提供进一步的必要信息开发这种生物标志物作为临床试验入学的工具，准确的观察性研究阿尔茨海默氏病和痴呆症的临床护理。