Hippocampal activity and pathology in APOE-4 subjects

描述(由申请人提供)： 这项提议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)的特征和年轻参与者(年龄在45岁到60岁之间)在记忆负担任务中的海马体反应，这些参与者有AD的遗传风险，但还没有任何症状。它还试图确定疾病的最早迹象，以及疾病发展的预测因素。具有APOE-4等位基因的志愿者和年龄匹配的没有APOE-4等位基因的志愿者将接受功能磁共振成像，同时学习新的联系，这是一项先前已被证明激活海马体的任务。APOE-4等位基因是AD的已知风险因素。这些受试者将接受使用FDDNP的PET扫描，FDDNP是一种探针，优先附着在淀粉样斑块和神经原纤维缠结上，并允许对它们进行成像。这些图像将使用为此目的而设计的计算机应用程序在二维场中进行“展开”或描绘。这将允许识别和定位海马体内的特定激活。然后，将PET图像和fMRI图像叠加，以确定淀粉样斑块和神经原纤维缠结的定位是否对应于记忆任务中信号强度的增加，就像AD患者中看到的那样。

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.