Hippocampal activity and pathology in APOE-4 subjects

描述（由申请人提供）： 该提案的目标是探索神经元缠结和淀粉样蛋白斑块之间的关系，阿尔茨海默病（AD）的标志和年轻（45至60岁）参与者在记忆负荷任务期间的海马反应，这些参与者具有AD的遗传风险，但尚未出现任何AD症状。 它也试图确定疾病的最早迹象，以及发展疾病的预测因素。具有APOE-4等位基因（AD的一个已知风险因素）的志愿者和年龄匹配的无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，这项任务以前已被证明可以激活海马体。这些相同的受试者将接受使用FDDNP的PET扫描，FDDNP是一种优先附着在淀粉样斑块和神经纤维缠结上的探针，并允许它们成像。这些图像将被“展开”，或使用为此目的设计的计算机应用程序在二维领域中描绘。这将允许识别和定位海马体内的特定激活。PET图像和fMRI图像然后将以这样的方式叠加，即可以确定淀粉样蛋白斑块和神经元缠结的定位是否对应于AD患者在记忆任务期间所见的信号强度的增加。

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.