ALZHEIMER'S DIAGNOSIS: LEUKOCYTE MULTIGENE SYNDROME

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。这一建议的核心假设是，替代组织(白细胞)中的基因表达变化是疾病过程的初级或次要结果，可能不直接反映大脑中的基因表达，可用于形成阿尔茨海默病(AD)的整体多基因分类器。如果这一假设是正确的，这种代用品和外周组织的基因表达模式可能构成AD诊断特征的基础。这一建议是基于目前的文献以及调查人员获得的一些试点数据。本研究的目的如下：1)采集30例AD患者和30例年龄匹配的对照组的血白细胞。2)利用Affymetrix基因芯片微阵列技术，同时检测AD患者和对照组血液中白细胞转录的多达14,000个基因的表达水平。3)分析本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患者和年龄匹配的健康对照组的基因表达模式(多基因签名)。总共将招募60名受试者：30名确诊为可能AD的AD患者，以及30名年龄匹配的对照组受试者。所有受试者(AD患者和对照受试者)将通过Silberstein老龄化和痴呆症研究所阿尔茨海默病研究中心(ADRC)的临床核心资源进行招募。研究小组将获得知情同意，并在首次用药前从每个受试者身上采集15毫升血液样本。血液样本将被处理以分离和纯化白细胞，然后样本将在RNA纯化、cRNA合成和基因芯片杂交和扫描之前被存储。这项拟议研究的基因表达数据将通过方差分析检验，并通过使用分层聚类和监督学习算法进行分析。

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.