Diagnosis of Very Early Alzheimer’s Disease – Genetic、Cognitive、Molecular、Neuroimaging Biomarkers

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Project title/計畫英文名

Project Number/計畫編號

DOH100-TD-PB-111-TM021

Translated Name/計畫中文名

極早期阿茲海默症之診斷-基因、認知、分子、神經影像之生物標記

Project Principal Investigator/計畫主持人

MING-JANG CHIU

Co-Investigator(s)/共同執行人

TA-FU CHEN

Funding Organization

Ministry of Health and Welfare

Department/Unit

Neurology

Start date/計畫起

01-05-2011

Expected Completion/計畫迄

30-04-2012

摘要：就總計畫的目的而言，是在建立一個臨床研究平台，包括可以提供150名正常受試者、150名輕度知能障礙者的募集與追蹤，提供各種診斷工具，包括病史、臨床檢查、神經學檢查、神經心理檢查、與核磁共振造影檢查來提供其他子計畫發展各種生物標記量化的黃金標準。總計畫整合子計畫一的三年計劃的目的，本計畫有三個目標：首先，我們將尋找在TOMM40基因中的一個SNP, rs10524523的poly-T的長度和阿茲海默症病人的臨床症狀的關係。這個SNP最近被發現它poly-T的長度和阿茲海默症發病的年齡有相關。這個基因剛好位於APOE基因的5’端。我們除了要了解這個SNP poly-T的長度和年齡的關係外，我們也將探討它和神經心理測驗項目、神經影像MRI 以及FDG 和類澱粉正子攝影影像的關係。其次，我們的目標是嘗試去找尋少見的序列變化(sequence variant)和阿茲海默症的關係。在先期研究中我們會選定20位臨床確立的阿茲海默症病人以及對照組來定序，除了APOE以外我們將選取六個已經在白人人種發現和阿茲海默症相關的基因CLU, PICAM, EXOC3L2, BIN1, CR1 以及SORL1等。我們將使用高通量的定序技術，將所有的exon以及control region的序列定序完畢。發現有可疑的SNP，我們將會把所有參與者的DNA都做這個SNP的定型(genotype)。有了這些基因的資料，我們又可以分析這些基因型和阿茲海默症以及相關臨床症狀的關係。這些基因危險因子的發現和了解，使我們對於疾病的預期和將來的藥物或疫苗的療效有更深的認識。
Abstract: The purpose of this integrated project is to provide a clinical research platform to recruit 150 normal subjects and 150 patients with mild cognitive impairment or very early Alzheimer’s disease. We intend to offer support of clinical history, examination, neuropsychological tests and MRI to serve as a clinical golden standard for other sub-projects. As for the genetic subproject, the puroposes of the three-year project are to explore the genetic risk factors contributing to late-onset Alzheimer’s disease (LOAD) and the correlation between the genotypes and the clinical features. There are three aims for the project. The first would be the exploration of the relationship between length of poly-T repeat of rs10524523 and the traits of LOAD. The genetic markers around the APOE gene which demonstrates the strongest contributing effect to LOAD would also be examined. In the second year, we would seek the rare sequence variants from six associated genes, CLU, PICAM, EXOC3L2, BIN1, CR1 and SORL1 using the second-generation sequencing methodology. The collapsed SNPs from either the same gene or multiple genes would then be subjected to analyze to see whether any correlation between the series of SNPs and the clinical features. These findings would be helpful for us to understand the molecular pathology and pathogenesis for LOAD. Specific genotype in susceptible genes could be employed in the clinical screening and as the basis for pharmacogenetics.

Keyword(s)

生物標記
阿茲海默症
特殊基因型
Biomarker
Alzheimer’s disease
genomics

DSpace CRIS

Diagnosis of Very Early Alzheimer’s Disease – Genetic、Cognitive、Molecular、Neuroimaging Biomarkers

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