PLASMA A BETA AS A SURROGATE GENETIC MARKER FOR LOAD

血浆 A Beta 作为负荷的替代遗传标记

• 批准号: 6846272
• 负责人: STEVEN G YOUNKIN
• 金额: $ 34.81万
• 依托单位: MAYO CLINIC ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-03-15 至 2007-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6846272
• 关键词: Alzheimer' s disease; amyloid proteins; blood proteins; clinical research; disease /disorder onset; disease /disorder proneness /risk; family genetics; gene mutation; genetic markers; genetic polymorphism; human subject; linkage mapping; molecular cloning; quantitative trait loci

DESCRIPTION: The identification of mutations in the APP, PS1, and PS2 genes that cause early-onset familial Alzheimer's disease (AD), the demonstration that these mutations all increase Abeta42, and the discovery of an association between Apolipoprotein E4 and late-onset Alzheimer's disease have dramatically improved our understanding of Alzheimer's disease. It is clear, however, that much of the genetic risk in late onset Alzheimer's disease remains unexplained. Current strategies to identify other genes that affect late-onset Alzheimer's disease have met with limited success often because of the difficulty associated with obtaining late-onset families with sufficient power for reliable linkage analysis. Genetic studies using large numbers of small families or sib-pairs, to increase the power of the analysis, are also currently being performed by several groups however difficulties with the non-replication of positive loci, identified by different studies, has continued. It will also be difficult to identify the biologically relevant genetic variability using loci identified by this type of small family/sib pair analysis, as candidate regions tend to be large and poorly defined. In this proposal we describe how high plasma ABeta levels can be used as a surrogate phenotype to increase the power of late-onset AD families allowing not only the reliable linkage of a specific chromosomal region with disease but also facilitating the identification of the genetic variability that is responsible for the increased plasma Abeta42 and for the increased risk of developing Alzheimer's disease.

描述：应用程序，PS1和PS2基因中突变的识别 这会导致早期发作的家族性阿尔茨海默氏病（AD），示范 这些突变都增加了Abeta42，并且发现了关联 载脂蛋白E4和阿尔茨海默氏症晚期疾病之间有着巨大的 提高了我们对阿尔茨海默氏病的理解。但是很明显， 阿尔茨海默氏病晚期的大部分遗传风险仍无法解释。 当前识别影响晚期阿尔茨海默氏症的其他基因的策略 由于困难，疾病经常取得有限的成功 与获得足够功能的晚期家庭有关 可靠的链接分析。使用大量小的遗传研究 为了增加分析的力量，家庭或同胞是 目前是由几个小组进行的 通过不同的研究确定的非阳性基因座的不复制已有 持续。也很难识别生物学相关的 使用这种类型的小型家庭/SIB对确定的基因座的遗传变异性 分析，因为候选区域往往很大且定义较差。 在此提案中，我们描述了如何将高血浆Abeta水平用作 替代表型增加了晚期广告系列的力量，允许 不仅是特定染色体区域与疾病的可靠联系，而且 还促进识别遗传变异性 负责增加的血浆Abeta42，并增加 发展阿尔茨海默氏病。