ALZHEIMER'S DIAGNOSIS: LEUKOCYTE MULTIGENE SYNDROME

阿尔茨海默病的诊断：白细胞多基因综合征

• 批准号: 7378344
• 负责人: JAMES Donald CLELLAND
• 金额: $ 1.82万
• 依托单位: NEW YORK UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-04-01 至 2007-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7378344
• 关键词: ALZHEIMER; DIAGNOSIS; LEUKOCYTE; MULTIGENE; SYNDROME

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The central underlying hypothesis in this proposal is that gene expression changes in a surrogate tissue (leukocytes), induced either as a primary or secondary result of the disease processes, and which may not directly reflect gene expression in the brain, can be utilized to form an overall multi-gene classifier of Alzheimer's disease (AD). If this hypothesis is correct, the pattern of gene expression from this surrogate, peripheral tissue could form the basis of a diagnostic signature of AD. This proposal is based on the current literature plus some pilot data the investigators have obtained. The objectives of the study are as follows: 1) To collect blood leukocytes from 30 AD patients and 30 age-matched control subjects over the two-year period of this project. 2) Employ Affymetrix GeneChip micro-array technology to measure simultaneously the expression levels of up to 14,000 genes transcribed in leukocytes derived from the blood of the AD patient and control subjects. 3) To analyze the leukocyte gene expression datasets collected during this proposal, using hierarchical clustering and supervised learning algorithms to identify and validate patterns of gene expression (multi-gene signatures) that differentiate AD subjects from age-matched healthy controls. A total of 60 subjects will be recruited: 30 AD patients with a confirmed diagnosis of probable AD, and 30 age-matched control subjects. All subjects (both AD patients and control subjects) will be recruited though the Clinical Core Resource within the Alzheimer's Disease Research Center (ADRC), Silberstein Institute for Aging and Dementia. The study team will obtain informed consent, and a 15ml blood sample will be collected from each subject prior to initial medication. Blood samples will be processed to isolate and purify the leukocytes and the samples will then be stored prior to RNA purification, cRNA synthesis and GeneChip hybridization and scanning. Gene Expression data from the proposed study will be analyzed by ANOVA testing, and by employing hierarchical clustering, and supervised learning algorithms.

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。在这个建议的核心基本假设是，在替代组织（白细胞）的基因表达的变化，诱导作为一个主要或次要的疾病过程的结果，可能不直接反映基因表达在大脑中，可以用来形成一个整体的多基因分类阿尔茨海默氏病（AD）。如果这一假设是正确的，那么来自该替代外周组织的基因表达模式可以形成AD诊断特征的基础。这一建议是基于目前的文献和研究人员获得的一些试点数据。本研究的目的如下：1）收集30例AD患者和30例年龄匹配的对照者的血液白细胞。2)采用Affyscore基因芯片微阵列技术，同时测量AD患者和对照受试者血液中白细胞中转录的多达14，000个基因的表达水平。3)为了分析在该提案期间收集的白细胞基因表达数据集，使用分层聚类和监督学习算法来识别和验证区分AD受试者与年龄匹配的健康对照的基因表达模式（多基因签名）。 共招募60例受试者：30例确诊为可能AD的AD患者和30例年龄匹配的对照受试者。所有受试者（AD患者和对照受试者）将通过阿尔茨海默病研究中心（ADRC）、Silberstein老龄和痴呆研究所的临床核心资源招募。研究团队将获得知情同意书，并在首次给药前采集每例受试者的15 ml血液样本。将处理血液样本以分离和纯化白细胞，然后在RNA纯化、cRNA合成和基因芯片杂交和扫描之前储存样本。将通过ANOVA检验、采用分层聚类和监督学习算法分析来自所提议研究的基因表达数据。