Targeting Lewy Body Specific Pathology Using Biomarkers

使用生物标志物针对路易体特异性病理学

基本信息

批准号：
9272132
负责人：
LAWRENCE S HONIG
金额：
$ 77.27万
依托单位：
COLUMBIA UNIVERSITY HEALTH SCIENCES
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-09-30 至 2021-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9272132
关键词：
African American Aging Alzheimer&apos s Disease Area Autopsy Biological Biological Assay Biological Markers Biology Blood Brain Brain region Cells Cerebrospinal Fluid Clinical Communities DNA DNA Methylation DNA Sequence Data Data Set Dementia Diagnosis Disease Early Diagnosis Early identification Enrollment Enzyme-Linked Immunosorbent Assay Epigenetic Process Evaluation Freezing Gene Expression Genes Genetic Genetic Transcription Haplotypes Height Heterogeneity Hispanic Americans Hispanics Impaired cognition Lewy Bodies Lewy Body Dementia Lewy Body Disease Longitudinal Studies Measures Methodology Methylation Molecular Profiling Molecular Target Movement Disorders National Institute of Neurological Disorders and Stroke Nerve Degeneration Neuraxis Neurons Parkinson Disease Parkinson&apos s Dementia Pathology Patients Phenotype Plasma Plasma Proteins Primary Health Care Protein Analysis Proteins RNA Recruitment Activity Research Resources Risk Sampling Series Staging Therapeutic Intervention Tissues Transcript Universities Washington abstracting base bead chip bisulfite bisulfite sequencing brain tissue caucasian American cell free DNA clinical Diagnosis clinical care cohort design diagnostic biomarker differential expression disorder control ethnic diversity exosome genome wide association study improved member methylation pattern metropolitan mind control molecular targeted therapies programs protein biomarkers specific biomarkers symposium targeted treatment therapeutic target transcriptome sequencing

项目摘要

Project Summary/Abstract Lewy body disorders include Parkinson’s Disease Dementia (PDD) and Dementia with Lewy Bodies (DLB). DLB is particularly problematic since it is often not appreciated until late stages, and often is admixed pathologically with concomitant Alzheimer’s disease (AD). Clinical care and the design of symptomatic and disease modifying trials for DLB would benefit from earlier diagnosis and reduced pathological heterogeneity. Thus, it is important to identify the extent to which Lewy Body versus AD pathology contributes to the phenotype and underlying biology of DLB, and to discover new molecular targets that specific to DLB. Clinically, we are uniquely poised to recruit a multiethnic cohort of DLB patients derived from both the local /metropolitan community, the Alzheimer’s Disease Research Center [ADRC], and the broader practice settings of the Aging and Dementia, Movement Disorders, and primary care programs at Columbia University. We will capture the continuum of cognitive impairment and extrapyramidal signs that exist in DLB. In Aim 1, we will identify and recruit an ethnically diverse (White, Hispanic, African American) cohort of 40 DLB patients per year for years 1-4, who will be followed semi-annually. We will administer the NINDS Parkinson’s Disease Biomarkers Program (PDBP) battery, the NIA National Alzheimer Coordinating Center (NACC) UDS3 with the new DLB module. In Aim 2, we will perform RNA gene expression and epigenetic (DNA methylation) profiling on dissected brain tissue from our Columbia University brain bank including cases with pathologically defined Lewy Body Disease with AD pathology (DLB/AD) and without significant AD (DLB), cases with AD, and controls to identify Lewy body specific differences primarily by comparing DLB/AD and AD. In Aim 3, we will use expression data from Aim 2, to develop biomarker assays in blood and CSF, including at RNA and protein levels. This aim will first utilize plasma from cases who have autopsy proven diagnosis, and will then be expanded to samples with clinical diagnoses.

项目摘要/摘要路易的身体疾病包括帕金森氏病痴呆症（PDD）和痴呆症身体（DLB）。 DLB尤其有问题，因为直到后期阶段通常才被欣赏，并且通常会在病理上与同时的阿尔茨海默氏病（AD）混合。临床护理 DLB的有症状和疾病修饰试验的设计将从早期受益诊断和病理异质性降低。这是重要的是要确定 Lewy身体与AD病理学有助于表型和潜在的生物学 DLB，并发现特定于DLB的新分子靶标。临床上，我们是独特的被毒死以招募来自本地 /大都市的DLB患者的多民族队列社区，阿尔茨海默氏病研究中心[ADRC]和更广泛的实践衰老和痴呆症，运动障碍和初级保健计划的设置哥伦比亚大学。我们将捕获认知障碍和腹膜外的连续体 DLB中存在的标志。在AIM 1中，我们将确定并招募一种种族多样的（白人， 1 - 4年的西班牙裔，非裔美国人）每年有40名DLB患者，他们将是每半年跟随。我们将管理Ninds帕金森氏病生物标志物计划（PDBP）电池，NIA国家阿尔茨海默氏症协调中心（NACC）UDS3 新的DLB模块。在AIM 2中，我们将执行RNA基因表达和表观遗传学（DNA）甲基化）分析我们哥伦比亚大学脑库解剖的脑组织包括患有病理定义的Lewy身体疾病的病例（DLB/AD）并且没有明显的AD（DLB），具有AD的病例和对照来识别特定于Lewy的身体差异主要是通过比较DLB/AD和AD。在AIM 3中，我们将使用来自 AIM 2，开发血液和CSF的生物标志物测定，包括在RNA和蛋白质水平上。这 AIM将首先利用具有尸检诊断的病例的等离子体，然后将是扩展到具有临床诊断的样品。