Alzheimer Biomarker Consortium - Down Syndrome (ABC-DS) - Supplement

阿尔茨海默病生物标志物联盟 - 唐氏综合症 (ABC-DS) - 补充材料

• 批准号: 10833788
• 负责人: Bradley T Christian
• 金额: $ 43.88万
• 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/10833788
• 关键词: Administrative Supplement; Adult; Age; Age of Onset; Alleles; Alzheimer' s Disease; Alzheimer' s disease related dementia; Alzheimer' s disease risk; Alzheimer’s disease biomarker; Amyloid; Amyloid beta-Protein Precursor; Biological Markers; Biology; Cerebrum; Chromosome 21; Clinical; Clinical Markers; Cognitive; Cross-Sectional Studies; Data; Data Set; Dementia; Diagnosis; Disease Progression; Down Syndrome; Elderly; Enrollment; Evaluation; Funding; Future; Gait; Gait speed; General Population; Genes; Genetic; Health; Health Promotion; Individual; Intervention; Life Style; Measures; Neuropsychology; Onset of illness; Participant; Pathology; Persons; Pharmacological Treatment; Population; Prevalence; Prevention trial; Production; Protein Precursors; Protocols documentation; Public Health; Research; Research Personnel; Sample Size; Senile Plaques; Site; Stimulus; Symptoms; System; Testing; Time; Visit; Work; abeta deposition; aging population; apolipoprotein E-4; clinical biomarkers; cognitive function; cohort; comorbidity; dementia risk; high risk; interest; middle age; mild cognitive impairment; neuropathology; power analysis; pre-clinical; tool; virtual

Abstract Alzheimer disease (AD) is the most common cause of dementia in the general population and the number of people living with AD is increasing rapidly. As the focus of pharmacologic treatment of AD has shifted toward prevention trials, there has been increased interest in individuals who have biomarkers (e.g., the ApoE4 allele) that place them at greater risk for dementia. One group of particular interest is adults with Down syndrome (DS), almost all of whom will be diagnosed with AD by the age of 70. Virtually all people with DS develop significant AD neuropathology, especially amyloid plaques by middle age. Early accumulation of amyloid plaques is thought to arise from overproduction of AE, which is derived from the E-amyloid precursor protein; the gene for E-amyloid precursor protein (APP) is located on the trisomic chromosome 21. While the mean age for developing AD among adults with DS is approximately 53 years, there is considerable variability in the age of onset, ranging from prior to age 40 to over age 70. Therefore, other factors such as genetics, lifestyle, and comorbid health issues likely contribute to the age of individual AD onset. In this supplement, “The ABC-DS: Administrative Supplement on Gait,” we propose to leverage the currently funded Alzheimer's Biomarker Consortium – Down Syndrome study (ABC-DS) to pilot a project focusing on gait as a possible clinical biomarker for dementia in the DS population. We propose to conduct a cross-sectional study using state-of-the-art assessment of dual-task gait measures among a cohort of 140 individuals with DS who are serving as participants in the ABC-DS. The ABC-DS has been following over 400 adults with DS since 2015 and was recently re-funded to increase this cohort to 550 individuals. Results will demonstrate the feasibility of conducting gait assessments across ABC-DS sites and to compare the findings with other AD biomarkers. In addition, this will provide the opportunity to assess additional dual-tasks that may be more sensitive across the entire IQ range (i.e., borderline to severe ID) and to provide the necessary pilot data to conduct a power analysis for a future R01 submission. Finally, the pilot will provide a rich dataset that can be shared and made available to other researchers and permit the testing of hypotheses related to the Projects in U19AG068054.

摘要 阿尔茨海默病（AD）是一般人群中痴呆症的最常见原因， 患有AD的人正在迅速增加。随着AD药物治疗的重点转向 在预防试验中，对具有生物标志物（例如，ApoE 4等位基因） 使他们患痴呆症的风险更大。一个特别感兴趣的群体是患有唐氏综合症（DS）的成年人， 几乎所有人在70岁时都会被诊断出患有AD。事实上，所有患有DS的人都会发展出显著的 AD神经病理学，尤其是中年淀粉样斑块。淀粉样斑块的早期积累是 被认为是由AE的过度产生引起的，AE来源于E-淀粉样前体蛋白; 淀粉样前体蛋白（APP）位于21号三体染色体上。而平均年龄为 在患有DS的成年人中，发生AD的年龄约为53岁， 发病年龄从40岁以前到70岁以上。因此，其他因素，如遗传，生活方式， 共病的健康问题可能有助于个体AD发病的年龄。 在这份补充材料中，“ABC-DS：步态管理补充材料”，我们建议利用目前的 资助阿尔茨海默病生物标志物联盟-唐氏综合症研究（ABC-DS）试点一个重点关注步态的项目 作为DS人群中痴呆症的可能临床生物标志物。我们建议进行一次横向调查 一项在140名DS患者队列中使用最新技术评估双任务步态测量的研究 他们是ABC-DS的参与者。ABC-DS自2010年以来一直在跟踪400多名患有DS的成年人。 2015年，最近重新资助，将这一群体增加到550人。结果将证明可行性 在ABC-DS研究中心进行步态评估，并将结果与其他AD生物标志物进行比较。在 此外，这将提供机会，以评估其他双重任务，可能是更敏感的整个 整个IQ范围（即，临界到严重ID），并提供必要的导频数据进行功率分析 未来的R 01提交。最后，试点将提供一个丰富的数据集，可以共享和提供 并允许测试与U19 AG 068054中的项目相关的假设。