Epidemiology of Biomarkers of Risk and Progression in LOAD

LOAD 风险和进展生物标志物的流行病学

• 批准号: 7908090
• 负责人: RICHARD P MAYEUX
• 金额: $ 197.84万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-05-01 至 2015-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7908090
• 关键词: Address; African American; Age; Aging; Agreement; Alzheimer' s Disease; Amyloid; Apolipoprotein E; Atrophic; Biochemical; Biological; Biological Markers; Blood; Blood Pressure; Blood Vessels; Blood specimen; Brain; Brain Diseases; Brain imaging; C-reactive protein; Cardiovascular system; Caribbean region; Cells; Cerebrovascular Circulation; Cerebrovascular Disorders; Clinical; Cognitive; Communities; DNA; Data; Data Collection; Databases; Dementia; Disease; Disease Pathway; Disease Progression; Elderly; Emotional; Environmental Health; Epidemiologic Studies; Epidemiology; Ethnic group; Family history of; Frequencies; Funding; Genetic; Genotype; Gonadal Steroid Hormones; Health; Height; Hippocampus (Brain); Hispanics; Homocysteine; Homocystine; Image; Impaired cognition; Individual; Insulin; Insulin Resistance; Investigation; Late Onset Alzheimer Disease; Lipids; Liquid substance; Magnetic Resonance Imaging; Measurable; Measurement; Measures; Medial; Medical; Memory; Methods; Molecular; Nerve Degeneration; Neurologic; Non-Insulin-Dependent Diabetes Mellitus; Not Hispanic or Latino; Obesity; Onset of illness; Outcome; Parietal Lobe; Participant; Pathway interactions; Pattern; Peptides; Performance; Pittsburgh Compound-B; Plasma; Positron-Emission Tomography; Prevalence; Principal Investigator; Procedures; Protein C; Public Health; Reporting; Research; Resources; Risk; Risk Factors; Sampling; Senile Plaques; Series; Speed; Stroke; Time; Washington; adiponectin; amyloid peptide; base; brain volume; cerebral atrophy; cerebrovascular; cohort; design; disorder risk; ethnic difference; frontal lobe; genetic risk factor; healthy aging; human tissue; in vivo; indexing; mild neurocognitive impairment; neuropsychological; prevent; programs; prospective; public health relevance; repository; trend; white matter

DESCRIPTION (provided by applicant): The overall theme of this new project is to establish and validate blood- and imaging-based biomarkers associated with the risk and progression of late onset Alzheimer's disease (LOAD), mild cognitive impairment (MCI) and the rate of cognitive decline in late life. We also propose to develop a framework with which we can understand how biomarkers interact and how they fit into the temporal sequence from healthy aging to dementia. This proposal is built on two decades of epidemiological research and systematic data collection in the multi-ethnic, Washington Heights, Hamilton Heights, Inwood, Columbia Aging Project (PO1AG07232). Over the past 20 years, we have investigated the rates of LOAD, MCI and cognitive decline in this urban community in northern Manhattan. We have investigated environmental, health-related and genetic risk factors of disease and predictors of disease progression by collecting longitudinal data on cognitive performance, emotional health, independence in daily activities, blood pressure, anthropometric measures, cardiovascular status and selected biomarkers in this elderly, multi-ethnic cohort, including lipids, amyloid peptides, sex hormones, homocysteine, insulin and C-reactive protein (CRP), and MRI. We have reported that the rates of disease and the frequency of disease risk factors vary across ethnic groups. We have identified one of the largest, multi-ethnic groups of incident LOAD cases facilitating studies of disease progression. Clinical and genetic data as well as biological resources are present for several thousand individuals. Biomarkers, cellular, biochemical or molecular alterations measurable in human tissues, cells, or fluids or by radiological means, are typically chosen because they are directly or indirectly in the causal pathway of disease. The emergence of structural and functional brain imaging has revolutionized epidemiological studies, particularly those using biomarkers for Alzheimer's disease. Positron emission tomography brain imaging using 11C Pittsburgh compound B is considered an in vivo measure of brain amyloid plaque load, while structural MRI, especially changes in brain volume and cerebral blood flow (CBF), can be considered an in vivo measures of neurodegeneration. In this new proposal, we will focus this longitudinal investigation on two sets of blood biomarkers that not only show consistent and robust associations to the risk of LOAD, MCI and cognitive decline, but that address the putative mechanisms related to amyloid burden and insulin resistance. We will take full advantage of the prospective design in this multi-ethnic cohort and the clinical, biological and brain imaging data collected to address six major hypotheses. The first two primary specific aims consider blood biomarkers as not only predictors of cognitive decline, MCI, LOAD and LOAD progression, but also as intermediate steps in the disease pathway, including neurodegeneration and cerebrovascular burden (MRI) and amyloid plaque load (PIB). In the last primary specific aim, brain imaging variables are predictors and cognitive decline, MCI, LOAD as well as LOAD progression are main outcomes. PUBLIC HEALTH RELEVANCE: There is general agreement that developing biomarkers that measure the risk of cognitive decline, LOAD and related diseases as well as the rate of disease progression would greatly enhance clinical, epidemiological, and pharmacological research. Furthermore developing biomarkers that can be easily obtained using standard and acceptable medical procedures such as blood samples or brain imaging would facilitate their use in developing methods to delay or prevent disease in the general community. Therefore the potential public health impact of developing reliable and valid biomarkers in a multi-ethnic community is a major benefit of this proposed investigation.

描述（由申请人提供）：这个新项目的总体主题是建立和验证基于血液和成像的生物标志物，与晚期发作的阿尔茨海默氏病的风险和进展相关（负载），轻度认知障碍（MCI）和晚期认知能力下降的速度。我们还建议开发一个框架，我们可以了解生物标志物如何相互作用，以及它们如何适应从健康衰老到痴呆的时间序列。该提案建立在二十年的流行病学研究和系统数据收集中，在华盛顿高地，汉密尔顿高地，哥伦比亚州老化项目（PO1AG07232）中。在过去的20年中，我们调查了曼哈顿北部这个城市社区的负载，MCI和认知能力下降的速度。我们通过收集有关认知表现，情绪健康，日常活动独立，血压，人体测量指标，心血管疾病状态和选定的生物标志物的纵向数据来研究疾病的环境，与健康有关的疾病和疾病进展的预测因素以及疾病进展的预测。 C反应蛋白（CRP）和MRI。我们报道说，疾病的发生率和疾病危险因素的频率在各个族群之间各不相同。我们已经确定了促进疾病进展研究的最大的多种事件载荷案例之一。数千名个人存在临床和遗传数据以及生物资源。 通常选择在人体组织，细胞或流体或放射线手段的生物标志物，细胞，生化或分子改变，因为它们是直接或间接在疾病的因果途径中，因此之所以选择。结构和功能性脑成像的出现彻底改变了流行病学研究，尤其是那些使用生物标志物进行阿尔茨海默氏病的研究。正电子发射断层扫描使用11C匹兹堡化合物B被认为是脑淀粉样斑块负荷的体内度量，而结构MRI，尤其是脑体积和脑血流量（CBF）的变化，可以认为是一种实际体内神经变性的量度。 在这项新提案中，我们将将这一纵向研究重点放在两组血液生物标志物上，它们不仅表现出与负载，MCI和认知能力下降的风险一致且牢固的关联，而且还针对与淀粉样蛋白负担和胰岛素抵抗相关的推定机制。我们将充分利用这种多民族队列以及收集的临床，生物学和脑成像数据的前瞻性设计，以解决六个主要假设。前两个主要特定目的将血液生物标志物视为认知下降，MCI，负荷进展的预测因素，而且还视为疾病途径的中间步骤，包括神经变性和脑血管负担（MRI）和淀粉样蛋白斑块负荷（PIB）。在最后一个特定目标中，大脑成像变量是预测因子和认知能力下降，MCI，负载以及负载进展是主要结果。 公共卫生相关性：普遍同意的是，开发生物标志物来衡量认知下降，负荷和相关疾病的风险以及疾病进展的速度将大大增强临床，流行病学和药理学研究。此外，开发可以使用标准和可接受的医疗程序（例如血液样本或脑成像）轻松获得的生物标志物，将有助于开发其在开发延迟或预防一般社区疾病的方法中的使用。因此，在多种族社区中发展可靠和有效的生物标志物的潜在公共卫生影响是这项拟议调查的主要好处。