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.

项目概要/摘要路易体疾病包括帕金森病痴呆 (PDD) 和路易体痴呆身体（DLB）尤其成问题，因为它通常直到后期才被重视，并且常常在病理上与伴随的阿尔茨海默氏病（AD）混合在一起。 DLB 的症状和疾病修饰试验的设计将受益于早期治疗诊断和减少病理异质性因此，确定其程度很重要。路易体与 AD 病理学有助于表型和基础生物学 DLB，并在临床上发现针对 DLB 的新分子靶点，我们是独一无二的。准备招募来自当地/大城市的多种族 DLB 患者队列社区、阿尔茨海默病研究中心 [ADRC] 以及更广泛的实践老龄化和痴呆症、运动障碍和初级保健项目的设置哥伦比亚大学。我们将捕捉认知障碍和锥体外系的连续体。 DLB 中存在的迹象在目标 1 中，我们将识别并招募不同种族的人（白人、（西班牙裔、非裔美国人）第 1-4 年每年 40 名 DLB 患者队列，他们将我们将每半年进行一次 NINDS 帕金森病生物标志物。计划 (PDBP) 电池、NIA 国家阿尔茨海默病协调中心 (NACC) UDS3 新的 DLB 模块在目标 2 中，我们将进行 RNA 基因表达和表观遗传（DNA）。对来自哥伦比亚大学脑库的解剖脑组织进行甲基化）分析包括病理学上明确的路易体病伴 AD 病理学 (DLB/AD) 的病例没有显着的 AD (DLB)、患有 AD 的病例以及用于识别路易体特异性的对照主要通过比较 DLB/AD 和 AD 来确定差异。在目标 3 中，我们将使用来自的表达数据。目标 2，开发血液和脑脊液中的生物标志物检测，包括 RNA 和蛋白质水平。目标将首先利用尸检证实诊断的病例的血浆，然后扩展到具有临床诊断的样本。