Core C: Clinical Core

核心 C：临床核心

基本信息

批准号：
10683429
负责人：
BENJAMIN L HANDEN
金额：
$ 78.87万
依托单位：
UNIVERSITY OF PITTSBURGH AT PITTSBURGH
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-09-30 至 2025-08-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10683429
关键词：
Adherence Adult Age Alzheimer&apos s Disease Alzheimer&apos s disease risk Alzheimer’s disease biomarker Amyloid Amyloid beta-Protein Amyloid beta-Protein Precursor Autopsy Biological Biological Markers Biometry Blood Caregivers Cataloging Chromosome 21 Classification Clinical Clinical Data Cognitive Collaborations Collection Communities Consensus Cross-Sectional Studies Data Data Collection Databases Dementia Development Disease Progression Down Syndrome Enrollment Ensure Evaluation Genes Genetic Goals Grant Health Health Status Individual MRI Scans Measures Modification Monitor Neurologic Examination Neuropsychology Participant Peptides Phenotype Policies Positron-Emission Tomography Procedures Proteomics Protocols documentation Puncture procedure Questionnaires Research Research Personnel Research Project Grants Sampling Senile Plaques Severities Siblings Site Visit Specimen Spinal Puncture Structure Symptoms Tissue Donations Training Underrepresented Minority Work abeta deposition amyloid peptide cohort data acquisition data management data sharing design disorder risk experience follow-up high risk informant lipidomics longitudinal analysis neuroimaging non-demented outreach overexpression performance site potential biomarker pre-clinical programs prospective recruit success symposium tau Proteins virtual

项目摘要

Clinical Core Abstract Virtually all adults with Down Syndrome (DS) have neuropathological changes consistent with Alzheimer Disease (AD) by age 40, including deposition of β amyloid peptide (Aβ) in diffuse and neuritic plaques, and most will develop clinical dementia by their late 60s.The high risk for AD has been attributed, at least in part, to triplication and overexpression of the gene for amyloid precursor protein (APP) on chromosome 21, leading to elevated levels of Aβ peptides The ABC-DS study is designed to understand the pathophysiological and clinical changes in adults with DS as they experience progression of AD from its earliest preclinical stages through frank dementia. The purpose of the Clinical Core is to provide participants with DS (and sibling controls), clinical data, and biological specimens to enable the goals of each project. This ultimately involves providing a best practice profile of abilities and health status to arrive at a valid clinical classification of dementia status. The Core will undertake the longitudinal assessment of a cohort of 720 individuals to maintain an active cohort of 550 adults with DS and 50 sibling controls. Over the course of this five-year project, participants will be seen for up to four evaluations (separated by 16 months). Data collection will include neuropsychological evaluations, caregiver questionnaires of functioning and possible dementia symptoms, a physical/neurological examination, blood for genetics, lipidomics and proteomics analyses, MRI and PET scans (amyloid, tau, FDG) and LP. The accumulating clinical data will be entered comprehensively into the ATRI database so it can be available for correlative analyses with the rich biological data generated from the same participants in Projects 1-3. The prospective clinical data will form the basis of cross sectional and longitudinal analyses of potential biomarkers and will enable the phenotypic correlations essential to understanding how they relate to disease risk, onset, severity, progression, and symptoms.

临床核心摘要几乎所有患有唐氏综合症 (DS) 的成年人都有与阿尔茨海默病一致的神经病理学变化 (AD) 到 40 岁时，包括 β 淀粉样肽 (Aβ) 在弥漫性斑块和神经炎斑块中沉积，大多数人会到 60 多岁时就会出现临床痴呆。AD 的高风险至少部分归因于三倍 21 号染色体上淀粉样前体蛋白 (APP) 基因的过度表达，导致 Aβ 肽水平 ABC-DS 研究旨在了解病理生理学和临床变化患有 DS 的成人患者经历 AD 从最早的临床前阶段到明显的痴呆的进展。临床核心的目的是为参与者提供 DS（和兄弟对照）、临床数据和生物样本以实现每个项目的目标这最终涉及提供最佳实践概况。核心将进行能力和健康状况的评估，以得出有效的痴呆状态临床分类。对 720 名个体的队列进行纵向评估，以维持 550 名 DS 成人的活跃队列， 50 个兄弟对照在这个为期五年的项目过程中，参与者将接受最多四次评估。（间隔 16 个月）。数据收集将包括神经心理学评估、护理人员。功能和可能的痴呆症状、身体/神经学检查、血液遗传学检查、脂质组学和蛋白质组学分析、MRI 和 PET 扫描（淀粉样蛋白、tau、FDG）和 LP。数据将全面输入 ATRI 数据库，以便可用于与项目 1-3 中相同参与者生成的丰富生物数据将产生前瞻性临床数据。形成潜在生物标志物横断面和纵向分析的基础，并将使表型相关性对于理解它们与疾病风险、发病、严重程度、进展和疾病的关系至关重要症状。