Characterization of Dementia with Lewy Bodies: A Collaborative Study

病理诊断为阿尔茨海默病（Alzheimer's disease，AD）的患者中，黑质外部位的o_-synuclein免疫组化检测发现，约30 ~ 60%的AD患者伴有路易体（Lewy body，LB）形成。这些患有AD/LB的患者，沿着以单独LB形成为特征的不太常见的痴呆，目前被归类为患有路易体痴呆（DLB）。在DLB患者中存在大量的临床和病理异质性，这阻碍了充分理解区分AD和DLB的意义的努力，并强烈提示在DLB患者中存在更多不同的亚组。 目前称为DLB。在这里，我们建议测试的假设，DLB不同于AD在临床，病理，分子遗传学和生化水平，这些相同的标准可以用来discem多个不同的亚组DLB。我们将在美国五个阿尔茨海默病中心（ADC）之间扩展一项已经运作的合作研究：俄勒冈州健康与科学大学，加州大学圣地亚哥分校，宾夕法尼亚大学，匹兹堡大学和华盛顿大学。我们建议从大约100名年龄匹配的对照组、250名AD患者和250名DLB患者中收集临床和神经病理学数据以及库存组织。我们估计收集20，50和50，分别为这个项目的每一年的额外情况。使用robust 通过对来自五个独立ADC的患者数据和材料的设计以及来自国家阿尔茨海默病协调中心（NACC）的生物统计学支持，我们将通过追求这些特定目标来测试我们的假设：通过确定（1）临床和病理学特征，（2）候选基因的特征，（3）氧化损伤的定量差异，和（4）tan、A[3]和β-突触核蛋白的可溶性和不溶性形式的改变。该项目的成功完成将巩固我们对DLB的理解，并为这第二种最常见的痴呆症的未来临床和分子研究提供基础。具体而言，该项目将建立一个国家DLB资源，包括临床病理数据数据库，以及DNA样本和冷冻脑组织的库存。这一资源将用于今后对DLB的调查。

Patients with the pathologic diagnosis of Alzheimer's disease (AD) commonly (approximately 30 to 60%) have concomitant Lewy body (LB) formation as detected with o_-synuclein immunohistochemical analysis of extra-nigral sites. These patients with AD/LB, along with a much less common dementia characterized by LB formation alone, are currently classified as having Dementia with Lewy Bodies (DLB). There is substantial clinical and pathologic heterogeneity among patients with DLB, thwarting efforts to understand fully the significance of distinguishing AD from DLB and strongly suggesting further distinct subgroups within what is currently called DLB. Here we propose to test the hypothesis that DLB differs from AD at clinical, pathologic, molecular genetic, and biochemical levels, and that these same criteria may be used to discem multiple distinct subgroups of DLB. We will expand an already functioning cooperative study among five Alzheimer Disease Centers (ADC) across the United States: Oregon Health & Science University, University of California at San Diego, University of Pennsylvania, University of Pittsburgh, and University of Washington. We propose to collect clinical and neuropathological data as well as banked tissue from approximately 100 age-matched controls, 250 patients with AD, and 250 patients with DLB. We estimate collection of 20, 50, and 50, respectively, additional cases for each year of this project. Using the robust design of patient data and material from five separate ADCs and biostatistical support from the National Alzheimer's Coordinating Center (NACC), we will test our hypothesis by pursuing these specific aims: to distinguish controls, AD, and DLB, and as well as DLB subgroups by determining (1) clinical and pathological features, (2) characteristics of candidate genes, (3) quantitative differences in oxidative damage, and (4) alterations in both soluble and insoluble forms of tan, A[3, and (z-synuclein. Successful completion of this project will solidify our understanding of DLB and provide a foundation for future clinical and molecular studies of this second most common form of dementia. Specifically, this project will establish a National DLB Resource, including a database of clinico-pathologic data, as well as an inventory of DNA samples and frozen brain tissue. This resource will be made available for future investigations of DLB.