Characterization of Dementia with Lewy Bodies: A Collaborative Study

路易体痴呆的表征：一项合作研究

• 批准号: 7270443
• 负责人: Thomas J Montine
• 金额: $ 53.12万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-09-30 至 2009-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7270443
• 关键词: Abbreviations; Age; Alzheimer' s Disease; Amygdaloid structure; Amyloid; Amyloid beta-Protein; Apolipoprotein E; Arachidonic Acids; Biochemical; Biochemical Genetics; Brain Stem; California; Candidate Disease Gene; Cerebrospinal Fluid; Characteristics; Chromosomes, Human, Pair 17; Classification; Clinical; Clinical Management; Clinical dementia rating scale; Cognition; Collaborations; Collection; Commit; Communication impairment; DNA; Data; Databases; Dementia; Diagnosis; Disease; Docosahexaenoic Acids; Epitopes; Equipment and supply inventories; Experimental Models; FTD with parkinsonism; Formic Acids; Foundations; Freezing; Future; Gas Chromatography; Goals; Haplotypes; Health Sciences; Heterogeneity; Institutes; Investigation; Ions; Isoprostanes; Lewy Bodies; Lewy Body Disease; Linear Models; Link; MSMB gene; Mass Spectrum Analysis; Microtubule-Associated Proteins; Microtubules; Molecular; Molecular Genetics; Monitor; Monoclonal Antibodies; Multiple System Atrophy; Neuraxis; Neurofibrillary Tangles; Neurologic; Neurons; Neuropil Threads; Nomenclature; Oregon; Parkinson Disease; Pathologic; Patients; Pennsylvania; Peptides; Polymerase Chain Reaction; Principal Investigator; Progressive Supranuclear Palsy; Proteins; Protocols documentation; Psyche structure; Questionnaires; REM Sleep Behavior Disorder; RNA Recognition Motif; Rate; Registries; Resources; Sampling; Senile Plaques; Site; Sleep; Stroke; Subgroup; TPO gene; Testing; Tissue Banking; Tissues; United States; Universities; Washington; alpha synuclein; base; brain tissue; cooperative study; design; experience; formic acid; mild neurocognitive impairment; neocortical; neuropsychiatry; paired helical filament; programs; synuclein; tau Proteins

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.

病理诊断为阿尔茨海默病（AD）的患者（约30%至60%）通常伴有路易体（LB）形成，这是通过神经外部位的o_synuclein免疫组化分析检测到的。这些AD/LB患者，以及仅以LB形成为特征的较不常见的痴呆，目前被归类为路易体痴呆（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，并强烈建议进一步区分亚群

项目成果

Lewy body pathology in late-onset familial Alzheimer's disease: a clinicopathological case series.

晚发家族性阿尔茨海默病的路易体病理学：临床病理病例系列。

• DOI: 10.3233/jad-2006-9302
• 发表时间: 2006
• 期刊: Journal of Alzheimer's disease : JAD
• 作者: Tsuang,DebbyW;Riekse,RobertG;Purganan,KristinaM;David,AndrewC;Montine,ThomasJ;Schellenberg,GerardD;Steinbart,EllenJ;Petrie,EricC;Bird,ThomasD;Leverenz,JamesB
• 通讯作者: Leverenz,JamesB

Quantitative proteomics identifies surfactant-resistant alpha-synuclein in cerebral cortex of Parkinsonism-dementia complex of Guam but not Alzheimer's disease or progressive supranuclear palsy.

定量蛋白质组学在关岛帕金森病-痴呆症复合体的大脑皮层中发现了表面活性剂抗性α-突触核蛋白，但在阿尔茨海默氏病或​​进行性核上性麻痹中没有发现。

• DOI: 10.2353/ajpath.2007.070015
• 发表时间: 2007
• 期刊: The American journal of pathology
• 作者: Yang,Wan;Woltjer,RandallL;Sokal,Izabela;Pan,Catherine;Wang,Yan;Brodey,Mary;Peskind,ElaineR;Leverenz,JamesB;Zhang,Jing;Perl,DanielP;Galasko,DouglasR;Montine,ThomasJ
• 通讯作者: Montine,ThomasJ

Familial occurrence of dementia with Lewy bodies.

路易体痴呆有家族性发生。

• 发表时间: 2004
• 期刊: The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry
• 作者: Tsuang,DebbyW;DiGiacomo,Lillian;Bird,ThomasD
• 通讯作者: Bird,ThomasD