Reiman Eric M
Banner Alzheimer's Institute, Department of Psychiatry at the University of Arizona, Arizona Alzheimer's Consortium, Phoenix, Arizona 85006, USA.
Ann N Y Acad Sci. 2007 Feb;1097:94-113. doi: 10.1196/annals.1379.011.
My colleagues and I have been using positron emission tomography (PET) and magnetic resonance imaging (MRI) to detect and track the brain changes associated with Alzheimer's disease (AD) and normal brain aging in cognitively normal persons with two copies, one copy, and no copies of the apolipoprotein E (APOE) epsilon4 allele, a common AD susceptibility gene. In this review article, I consider how brain imaging techniques could be used to evaluate putative AD prevention therapies in cognitively normal APOE epsilon4 carriers and putative age-modifying therapies in cognitively normal APOE epsilon4 noncarriers, how they could help investigate the individual and aggregate effects of putative AD risk modifiers, and how they could help guide the investigation of a molecular mechanism associated with AD vulnerability and normal neurological aging. I suggest how high-resolution genome-wide genetic and transcriptomic studies could further help in the scientific understanding of AD, aging, and other common and genetically complex phenotypes, such as variation in normal human memory performance, and in the discovery and evaluation of promising treatments for these phenotypes. Finally, I illustrate the push-pull relationship between brain imaging, genomics research, and other neuroscientific research in the study of AD and aging.
我和我的同事们一直在使用正电子发射断层扫描（PET）和磁共振成像（MRI）技术，来检测和追踪认知正常人群中与阿尔茨海默病（AD）以及正常脑老化相关的脑部变化。这些认知正常的人群分别携带两份、一份以及不携带载脂蛋白E（APOE）ε4等位基因拷贝，APOEε4是一种常见的AD易感基因。在这篇综述文章中，我探讨了脑成像技术如何用于评估针对认知正常的APOEε4携带者的AD预防疗法以及针对认知正常的非APOEε4携带者的年龄调节疗法，它们如何有助于研究AD风险修饰因素的个体和总体效应，以及如何有助于指导与AD易感性和正常神经老化相关分子机制的研究。我还提出高分辨率全基因组遗传和转录组学研究如何能够进一步帮助我们从科学角度理解AD、衰老以及其他常见的、具有遗传复杂性的表型，比如人类正常记忆表现的差异，以及如何帮助发现和评估针对这些表型的有前景的治疗方法。最后，我阐述了在AD和衰老研究中脑成像、基因组学研究以及其他神经科学研究之间的推拉关系。
