Characterization of Dementia with Lewy Bodies: A Collaborative Study

病理诊断为阿尔茨海默病(AD)的患者通常(约30%至60%)伴有黑质外部位o-突触核素免疫组织化学分析所发现的路易小体(L B)形成。这些患有AD/LB的患者，以及一种不太常见的痴呆，其特征是单纯的LB形成，目前被归类为路易体痴呆(DLB)。DLB患者的临床和病理有很大的异质性，阻碍了充分了解区分AD和DLB的意义的努力，并强烈建议在什么情况下进一步区分不同的亚型 目前被称为DLB。在这里，我们建议检验这一假设，即DLB在临床、病理、分子遗传学和生化水平上与AD不同，并且这些相同的标准可用于区分DLB的多个不同亚型。我们将扩大美国五个阿尔茨海默病中心(ADC)之间已经在运作的合作研究，这五个中心是俄勒冈健康与科学大学、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。我们建议收集大约100名年龄匹配的对照组、250名AD患者和250名DLB患者的临床和神经病理学数据以及储存的组织。我们估计，这个项目每年分别收集20、50和50个额外的案例。使用健壮的 通过从五个不同的ADC设计患者数据和材料，以及来自国家阿尔茨海默病协调中心(NACC)的生物统计支持，我们将通过追求这些特定目标来检验我们的假设：通过确定(1)临床和病理特征，(2)候选基因的特征，(3)氧化损伤的数量差异，以及(4)可溶和不溶形式的tan、A[3和(z-突触核蛋白)的变化，来区分对照组、AD和DLB以及DLB亚组。该项目的成功完成将巩固我们对DLB的了解，并为这种第二种最常见的痴呆症的未来临床和分子研究提供基础。具体地说，该项目将建立一个国家DLB资源，包括一个临床病理数据数据库，以及DNA样本和冰冻脑组织的清单。这笔资源将用于未来对德意志银行的调查。

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.