Apolipoprotein E, Cognition, and Alzheimer's Disease

载脂蛋白 E、认知和阿尔茨海默病

• 批准号: 6533928
• 负责人: RAJA PARASURAMAN
• 金额: $ 38.46万
• 依托单位: CATHOLIC UNIVERSITY OF AMERICA
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-09-15 至 2006-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6533928
• 关键词: Alzheimer's disease; age difference; aging; apolipoprotein E; attention; behavioral /social science research tag; cooperative study; early diagnosis; evoked potentials; genetic carriers; human subject; memory; neuropsychological tests; patient oriented research

New methods for preventing, slowing the progression of, and treating Alzheimer's disease (AD) are urgently needed given the dramatic growth in the number of people afflicted with AD. Such efforts would be helped if AD could be detected in its preclinical stage, before irreversible brain changes occur. One approach, followed in the proposed research, is to examine individuals who are not demented but are at increased risk for developing AD due to inheritance of the epsilon4 allele of the apolipoprotein E gene (APOE) on chromosome 19. Nondemented persons with the APOE-epsilon4 genotype exhibit regional cerebral metabolic changes in association temporal, parietal, and frontal cortical areas that mirror those seen in mildly demented AD patients. These brain regions include distributed networks that mediate visuospatial attention and spatial working memory. The proposed research will therefore investigate the hypothesis that nondemented APOE-epsilon4 carriers have selective deficits in specific component processing operations underlying attention and memory. The goal is to investigate changes over time in preclinical AD in component operations of attention, working memory, and their neurobiological correlates, using information-processing tests, event-related brain potentials (ERPs), and biological markers (beta-amyloid and tau). These measures will be obtained in middle-aged nondemented adults genotyped for APOE, AD patients, and age-matched controls. A unique aspect of the research is the comprehensive approach to assessment of longitudinal changes, including behavioral, electrophysiological, and biological measures. Five studies are proposed, one large-scale study and four additional experiments. These studies will ascertain the cognitive impact of APOE in otherwise asymptomatic adults and will establish the relationship between changes in attention and working memory in preclinical and early AD. The results will have significant implications for the early detection of AD as well as for an understanding of the genetic basis of normal cognitive operations underlying attention and memory.

鉴于患有阿尔茨海默病 (AD) 的人数急剧增加，迫切需要预防、减缓其进展和治疗阿尔茨海默病 (AD) 的新方法。如果 AD 能够在临床前阶段、在不可逆的大脑变化发生之前被检测到，那么这些努力将会有所帮助。拟议研究中采用的一种方法是检查那些没有痴呆但由于 19 号染色体上的载脂蛋白 E 基因 (APOE) 的 epsilon4 等位基因遗传而导致患 AD 风险增加的个体。具有 APOE-epsilon4 基因型的非痴呆患者在颞叶、顶叶和额叶皮层区域表现出局部脑代谢变化，这与轻度中所见的情况相似。 痴呆症患者。这些大脑区域包括调节视觉空间注意力和空间工作记忆的分布式网络。因此，拟议的研究将调查以下假设：非痴呆 APOE-epsilon4 携带者在关注和记忆的特定组件处理操作中具有选择性缺陷。目标是利用信息处理测试、事件相关脑电位 (ERP) 和生物标志物（β-淀粉样蛋白和 tau）来研究临床前 AD 中注意力、工作记忆及其神经生物学相关性的组成部分随时间的变化。这些测量值将在进行 APOE 基因分型的中年非痴呆成年人、AD 患者和年龄匹配的对照中获得。该研究的一个独特方面是评估纵向变化的综合方法，包括行为、电生理和生物测量。提出了五项研究，一项大规模研究和四项附加实验。这些研究将确定 APOE 对其他无症状成人的认知影响，并将建立临床前和早期 AD 注意力变化和工作记忆之间的关系。这些结果将对 AD 的早期检测以及对注意力和记忆力正常认知运作的遗传基础的理解产生重大影响。