Apolipoprotein E, Cognition, and Alzheimer's Disease

载脂蛋白 E、认知和阿尔茨海默病

• 批准号: 6951806
• 负责人: RAJA PARASURAMAN
• 金额: $ 40.52万
• 依托单位: GEORGE MASON UNIVERSITY
• 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 2007-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6951806
• 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）的人数急剧增长，迫切需要用于预防、减缓AD的进展和治疗AD的新方法。如果在不可逆的大脑变化发生之前，在临床前阶段就能检测到AD，那么这些努力将有所帮助。在拟议的研究中遵循的一种方法是检查没有痴呆但由于19号染色体上载脂蛋白E基因（APOE）的ε 4等位基因遗传而导致AD风险增加的个体。具有APOE-ε 4基因型的非痴呆患者在颞叶、顶叶和额叶皮质区表现出局部脑代谢变化，这与轻度痴呆AD患者中观察到的变化相似。这些大脑区域包括介导视觉空间注意力和空间工作记忆的分布式网络。因此，拟议中的研究将调查这一假设，即非痴呆APOE-ε 4携带者在特定的组件处理操作的基础上的注意力和记忆的选择性缺陷。目的是研究临床前AD在注意力、工作记忆及其神经生物学相关性的组成部分操作中随时间的变化，使用信息处理测试、事件相关脑电位（ERP）和生物标志物（β-淀粉样蛋白和tau蛋白）。这些措施将在中年非痴呆成年人中获得APOE基因型，AD患者和年龄匹配的对照。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，电生理和生物措施。提出了五项研究，一项大规模的研究和四个额外的实验。这些研究将确定APOE在其他无症状成人中的认知影响，并将建立临床前和早期AD中注意力和工作记忆变化之间的关系。这些结果将对AD的早期检测以及理解注意力和记忆力的正常认知操作的遗传基础具有重要意义。

项目成果

Perceptual load interacts with involuntary attention at early processing stages: event-related potential studies.

知觉负荷与早期处理阶段的非自愿注意相互作用：事件相关潜力研究

• DOI: 10.1016/j.neuroimage.2009.06.028
• 发表时间: 2009-10-15
• 期刊: NEUROIMAGE
• 影响因子: 5.7
• 作者: Fu, Shimin;Huang, Yuxia;Luo, Yuejia;Wang, Yan;Fedota, John;Greenwood, Pamela M.;Parasuraman, Raja
• 通讯作者: Parasuraman, Raja

Neural correlates of age-related reduction in visual motion priming.

• DOI: 10.1080/13825580802348588
• 发表时间: 2009-03
• 期刊: Neuropsychology, development, and cognition. Section B, Aging, neuropsychology and cognition
• 作者: Jiang Y;Luo YJ;Parasuraman R
• 通讯作者: Parasuraman R

Both a nicotinic single nucleotide polymorphism (SNP) and a noradrenergic SNP modulate working memory performance when attention is manipulated.

• DOI: 10.1162/jocn.2008.21164
• 发表时间: 2009-11
• 期刊: Journal of cognitive neuroscience
• 影响因子: 3.2
• 作者: Greenwood PM;Sundararajan R;Lin MK;Kumar R;Fryxell KJ;Parasuraman R
• 通讯作者: Parasuraman R

Differential contributions of dorso-ventral and rostro-caudal prefrontal white matter tracts to cognitive control in healthy older adults.

• DOI: 10.1371/journal.pone.0081410
• 发表时间: 2013
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Strenziok M;Greenwood PM;Santa Cruz SA;Thompson JC;Parasuraman R
• 通讯作者: Parasuraman R

Perceptual load, voluntary attention, and aging: an event-related potential study.

• DOI: 10.1016/j.ijpsycho.2012.01.002
• 发表时间: 2012-04
• 期刊: INTERNATIONAL JOURNAL OF PSYCHOPHYSIOLOGY
• 影响因子: 3
• 作者: Wang, Yan;Fu, Shimin;Greenwood, Pamela;Luo, Yuejia;Parasuraman, Raja
• 通讯作者: Parasuraman, Raja