Hippocampal activity and pathology in APOE-4 subjects

APOE-4 受试者的海马活动和病理学

• 批准号: 6838722
• 负责人: Meredith Nicole Braskie
• 金额: $ 3.82万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-09-30 至 2006-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6838722
• 关键词: Alzheimer' s disease; amyloid proteins; apolipoprotein E; bioimaging /biomedical imaging; brain disorder diagnosis; brain imaging /visualization /scanning; clinical research; computer assisted diagnosis; computer program /software; early diagnosis; functional magnetic resonance imaging; genetic susceptibility; hippocampus; human middle age (35-64); human subject; memory disorders; neurofibrillary tangles; pathologic process; positron emission tomography; predoctoral investigator; psychological tests; sign /symptom; statistics /biometry

DESCRIPTION (provided by applicant): The goal of this proposal is to explore the relationship between neurofibrillary tangles and amyloid plaques, the hallmarks of Alzheimer's disease (AD) and the hippocampal response during a memory-taxing task in young (aged 45 to 60) participants who have a genetic risk for, but not yet any symptoms of AD. It is also to attempt to identify the earliest signs of the disease, and predictive factors for developing the disease. Volunteers, who have the APOE-4 allele, a known risk factor for AD, and their age-matched counterparts without APOE-4, will undergo functional magnetic resonance imaging while learning new associations, a task that previously has been shown to activate the hippocampus. These same subjects will undergo PET scans using FDDNP, a probe that attaches preferentially to amyloid plaques and neurofibrillary tangles and allows them to be imaged. The images will be "unfolded", or portrayed in a two-dimensional field, using a computer application designed for that purpose. This will allow specific activation within the hippocampus to be identified and localized. The PET images and fMRI images will then be superimposed in such a way that it will be possible to determine whether localization of amyloid plaques and neurofibrillary tangles correspond to increases in signal intensity during memory tasks as seen in AD patients.

描述（由申请人提供）： 该提案的目标是探索神经原纤维缠结和淀粉样斑块之间的关系、阿尔茨海默病 (AD) 的标志，以及具有阿尔茨海默病遗传风险的年轻参与者（45 至 60 岁）在执行记忆任务期间海马反应。 ，但还没有任何 AD 症状。 它还试图确定该疾病的最早迹象以及发生该疾病的预测因素。携带 APOE-4 等位基因（一种已知的 AD 危险因素）的志愿者，以及年龄匹配但不携带 APOE-4 的志愿者，将接受功能性磁共振成像，同时学习新的关联，这项任务之前已被证明可以激活海马体。这些受试者将使用 FDDNP 进行 PET 扫描，FDDNP 是一种优先附着在淀粉样斑块和神经原纤维缠结上的探针，并可对它们进行成像。使用为此目的设计的计算机应用程序，图像将被“展开”或在二维场中描绘。这将允许识别和定位海马体内的特定激活。然后，PET 图像和 fMRI 图像将以这样的方式叠加，从而可以确定淀粉样斑块和神经原纤维缠结的定位是否与 AD 患者在记忆任务期间看到的信号强度的增加相对应。