Core C: Clinical Core

核心 C：临床核心

• 批准号: 10454254
• 负责人: BENJAMIN L HANDEN
• 金额: $ 535.97万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 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/10454254
• 关键词: Adherence; Adult; Age; Alzheimer' s Disease; Alzheimer' 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; 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

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）的成年人都具有与阿尔茨海默氏病一致的神经病理学变化 （AD）到40岁，包括β淀粉样蛋白肽（Aβ）在弥漫性和神经斑中的沉积，大多数将 在60年代后期发展临床痴呆症。广告的高风险至少部分归因于一式三份 染色体上淀粉样蛋白前体蛋白（APP）的基因的过表达，导致升高 Aβ肽的水平ABC-DS研究旨在了解病理生理和临床变化 在患有DS的成年人中，他们从最早的临床前阶段经历了弗兰克痴呆症的发展。 临床核心的目的是为参与者提供DS（和兄弟姐妹控件），临床数据和 生物标本可以实现每个项目的目标。最终涉及提供最佳实践概况 能力和健康状况得出有效的痴呆状态临床分类。核心将承担 对720名个人的纵向评估，以维持550名成年人的活跃队列 50个同级控件。在这个五年项目的过程中，最多可供参与者进行四次评估 （分开16个月）。数据收集将包括神经心理学评估，护理人员问卷调查 功能和可能的痴呆症状，身体/神经检查，遗传学血液， 脂肪组学和蛋白质组学分析，MRI和PET扫描（淀粉样蛋白，TAU，FDG）和LP。积累的临床 数据将彻底输入到ATRI数据库中，因此可以与 来自项目1-3的同一参与者产生的丰富生物学数据。前瞻性临床数据将 构成潜在生物标志物的横截面和纵向分析的基础，并将实现表型 相关性对于了解它们与疾病风险，发作，严重程度，进步和 症状。