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.
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