IN VIVO PIB PET AMYLOID IMAGING: NORMALS, MCI & DEMENTIA

描述（由申请人提供）：该图显示了认知正常对照、阿尔茨海默病（AD）患者和轻度认知障碍（MCI）患者的匹兹堡化合物b （PiB）正电子发射断层扫描（PET）图像。这些图像没有按照所列的顺序显示，并且故意没有标记，以说明纤维状淀粉样蛋白- β （A¿）沉积物在大脑中的存在、数量和区域分布并不总是与认知功能相关。之前的死后研究已经证明了这一点，但体内淀粉样蛋白成像使我们能够以以前不可能的方式探索这种现象。从这个图中可以得出两个相反的结论：1)纤维A¿沉积与AD的认知功能障碍无关，或者2)纤维A¿沉积对认知的影响存在调节剂。为了充分了解AD的病理生理学，我们必须解决这个问题：“哪些因素决定了特定个体A¿沉积的影响？”衰老的大脑中最重要的两种疾病是阿尔茨海默病和血管疾病。许多研究表明，血管疾病可导致轻度认知障碍和痴呆。本项目更新申请旨在综合研究这两种疾病之间的相互关系，并研究血管疾病如何影响大脑AD病理个体症状的存在和进展速度。要找到这个重要问题的答案，需要将死后研究与体内研究相结合，在接近认知测试的时间范围内测量a¿及其潜在调节剂。我们有一个独特的机会对接受PiB-PET成像和详细临床评估的受试者进行死后分析。本项目的总体具体目标是：1)确定a¿和血管“调节变量”（包括系统和脑血管）的组合是否比单独a¿测量提高了对研究结果（即认知、脑代谢和萎缩）的预测；2)增加我们对PiB滞留的神经病理基础和体内检测A¿沉积的阈值的理解。

DESCRIPTION (provided by applicant): The figure shows Pittsburgh Compound-B (PiB) positron emission tomography (PET) images from a cognitively normal control, an Alzheimer's disease (AD) patient and a Mild Cognitive Impairment (MCI) patient. The images are not shown in the order listed and are intentionally not labeled to make the point that the presence, amount and regional distribution of fibrillar amyloid-beta (A¿) deposits in the brain do not always correlate with cognitive function. Postmortem studies have shown this previously, but in vivo amyloid imaging allows us to explore this phenomenon in ways that were not previously possible. Two opposing conclusions can be drawn from this figure: 1) either fibrillar A¿ deposition is not related to the cognitive dysfunction of AD or 2) there are modulators of the effects of fibrillar A¿ deposition on cognition. To fully understand the pathophysiology of AD, we must address the question: "Which factors determine the impact of A¿ deposition in a given individual?" Two of the most important diseases in the aging brain are AD and vascular disease. Many studies have shown that vascular disease can contribute to MCI and dementia. This Program Project renewal application proposes to take an integrative view on the inter-relationships between these two disorders and to examine how vascular disease may influence the presence and rate of progression of symptoms in individuals who have AD pathology in their brain. Finding the answer to this important question requires a combination of postmortem studies with in vivo studies to measure A¿ and its potential modulators in close temporal proximity to cognitive testing. We have a unique opportunity to perform postmortem analyses of subjects who underwent PiB-PET imaging and detailed clinical evaluation before death. The overall specific aims of this Program Project are to: 1) Determine whether a combination of A¿ and vascular "Modulating Variables" (both systemic and cerebrovascular) improves the prediction of the Study Outcomes (i.e., cognition, brain metabolism and atrophy) over A¿ measures alone; and 2) Increase our understanding of the neuropathological substrates of PiB retention and the threshold for in vivo detection of A¿ deposition.