PET, APOE & the Preclinical Course of Alzheimer's Disease

宠物、载脂蛋白

• 批准号: 8050044
• 负责人: ERIC MICHAEL REIMAN
• 金额: $ 128.66万
• 依托单位: BANNER ALZHEIMER'S INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-04-01 至 2013-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8050044
• 关键词: Affect; Alleles; Alzheimer' s Disease; Alzheimer' s disease risk; Amyloid deposition; Apolipoprotein E; Arizona; Biological; Blood specimen; Brain; Brain imaging; C-reactive protein; Cerebrum; Cholesterol; Clinical; Communities; DNA; Data; Disease susceptibility; Dose; Early Diagnosis; Evaluation; Foundations; Funding; Generations; Genes; Genetic; Genetic Risk; Genotype; Glucose; Heterozygote; Hispanics; Homocysteine; Homocystine; Homozygote; Image; Image Analysis; Impaired cognition; Individual; Institutes; Late Onset Alzheimer Disease; Latino; Longitudinal Studies; Magnetic Resonance Imaging; Measurement; Measures; Memory; Metabolic; Methods; Minority Groups; Network-based; Neuropsychological Tests; Persons; Pittsburgh Compound-B; Positron-Emission Tomography; Prevention therapy; Primary Prevention; Research; Research Personnel; Resources; Risk; Risk Factors; Sample Size; Serum; Single Nucleotide Polymorphism; Specimen; Staging; Susceptibility Gene; Techniques; Testing; Thick; base; brain volume; case control; cost effective; density; design; endophenotype; fluorodeoxyglucose positron emission tomography; genome wide association study; gray matter; improved; middle age; mild neurocognitive impairment; non-genetic; pre-clinical; programs; treatment effect

DESCRIPTION (provided by applicant): We request five years of continued support for the longitudinal study of 205 initially late-middle-aged, cognitively normal persons with two copies, one copy and no copies of the apolipoprotein E 54 allele, a common late-onset Alzheimer's disease (AD) susceptibility gene. During the next funding period, 1) we will continue to characterize and compare baseline measurements and longitudinal changes in fluorodeoxyglucose positron emission tomography (FDG PET) measurements of the cerebral metabolic rate for glucose (CMRgl), magnetic resonance imaging (MRI) measurements of gray matter density, cortical thickness and whole brain volume, clinical ratings and neuropsychological tests every two years in 35 54 homozygotes, 50 54 heterozygotes, and 75 54 non-carriers, further characterize their relationship to 54 gene dose, and determine the extent to which baseline brain-imaging measurements and longitudinal changes predict subsequent rates of cognitive decline and conversion to mild cognitive impairment (MCI) or probable AD; and we will continue to characterize and compare the same measurements in 15 54 carriers and 30 54 non-carriers from the Latino community to further establish the extent to which our findings are relevant to this understudied minority group. 2) We will also acquire PET measurements of the Pittsburgh Compound B Distribution Volume Ratio (PIB DV) every two years, providing a unique opportunity to detect and track the some of the earliest fibrillar amyloid deposition in cognitively normal persons at three levels of genetic risk for late-onset AD, characterize the relationship of fibrillar amyloid deposition to the other brain imaging changes in these individuals, and ultimately determine the extent to which fibrillar amyloid deposition, alone or in combination with other brain imaging measurements, predicts subsequent rates of cognitive decline and conversion to MCI and probable AD. 3) We will use our proposed presymptomatic brain-imaging endophenotype to evaluate putative modifiers of AD risk, including an aggregate genetic risk score and individual single nucleotide polymorphisms (SNPs) that we have implicated in an independently funded 500,000 SNP whole-genome association study of more than a thousand clinically and neuropathologically characterized AD cases and controls. 4) We will further refine, test and establish the value of advanced voxel-based image-analysis techniques in the unusually early detection and tracking of brain changes associated with the differential risk of AD. 5) Finally, we will continue to share our core resource of DNA, biological specimens, data and findings in support of other investigators and other studies. This study is ultimately intended to provide a cost-effective way to evaluate promising treatments for the primary prevention of AD. Indeed, we have established a new non-profit institute for this very purpose.

描述（由申请人提供）：我们要求对205个最初中期中期的纵向研究进行五年的持续支持，这些纵向，经认知正常的人，带有两份副本，一份副本和无副蛋白E 54等位基因，这是一种常见的晚期发作晚期的阿尔茨海默氏病（AD）usigantibility gene。在下一个资金期间，1）我们将继续表征和比较荧光脱氧葡萄糖正电子发射断层扫描（FDG PET）的基线测量以及葡萄糖代谢速率（CMRGL）的大脑代谢速率的测量值（CMRGL），磁性结合成像（MRI）的临床范围和整体均匀度量，整体量，整体量，整体量，整体均可体验，整体量每两年在35 54个纯合子，50 54个杂合子和75 54个非携带者中，进一步表征了它们与54个基因剂量的关系，并确定了基线的脑成像测量值和纵向变化的程度，预测了认知能力下降的速度和对轻度认知障碍的后续率（MCI MCI）或可能的随后降低（MCI MCI）；我们将继续表征和比较来自拉丁裔社区的15个54个载体和30 54个非携带者的相同测量值，以进一步确定我们的发现与这个研究不足的少数群体相关的程度。 2）我们还将每两年获得一次匹兹堡化合物B分布量比（PIB DV）的宠物测量值，提供一个独特的机会，可以在三个级别的遗传风险中检测和跟踪认知正常人中最早的原纤维淀粉样蛋白沉积在三个级别的遗传风险中，以表征纤维膜的范围，并确定了其他范围的范围，以确定这些范围的范围。原纤维淀粉样蛋白沉积，单独或与其他脑成像测量结果结合使用，可以预测认知能力下降和转化为MCI和可能的AD的速率。 3）我们将使用我们提出的预症状大脑成像的内表型评估AD风险的推定修饰符，包括总体遗传风险评分和单个单核苷酸多态性（SNP），我们与我们涉及的500,000个基金资助的500,000个SNP全基因组协会研究了数以千计的临床上和神经疗法的AD和对照序列，并对其进行了特征。 4）我们将进一步完善，测试并确定基于先进的体素图像分析技术在异常的早期检测和跟踪与AD差异风险相关的大脑变化中的价值。 5）最后，我们将继续共享我们的DNA，生物标本，数据和发现的核心资源，以支持其他研究人员和其他研究。这项研究最终旨在提供一种评估有希望的AD预防的有希望的治疗方法的方法。确实，我们为此目的建立了一个新的非营利研究所。