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.

抽象的 阿尔茨海默氏病（AD）是普通人群中痴呆的最常见原因，数量 与广告有关的人正在迅速增加。由于AD的药物治疗的重点已转向 预防试验，人们对具有生物标志物的个体（例如APOE4等位基因）的兴趣增加了 那使他们面临更大的痴呆症风险。一组特别感兴趣的是唐氏综合症（DS）的成年人， 几乎所有的人都将在70岁之前被诊断出患有广告。几乎所有患有DS的人都会发展出重要的 AD神经病理学，尤其是中期淀粉样蛋白斑块。淀粉样斑块的早期积累是 被认为是由AE产生的，AE的生产过量，该AE源自E-淀粉样蛋白的前体蛋白。基因 E-淀粉样蛋白前体蛋白（APP）位于Trisomic染色体21上。而平均年龄 DS成年人中开发广告大约53岁，年龄有很大的可变性 发作，从40岁到40岁到70岁以上。因此，遗传学，生活方式和 合并症的健康问题可能会导致个人广告发作的年龄。 在此补品中，我们建议在此补充“ ABC-DS：步态行政补充” 资助阿尔茨海默氏症的生物标志物联盟 - 唐氏综合症研究（ABC-DS），以试行一个针对步态的项目 作为DS人群痴呆症的可能临床生物标志物。我们建议进行横截面 使用对双重任务的最新评估的研究符合140名DS的人群中的措施 在ABC-DS中担任参与者。自从ABC-DS一直关注400多名成年人以来 2015年，最近被重新资助，将此队列增加到550个人。结果将证明可行性 跨ABC-DS站点进行AGGET评估，并将发现与其他AD生物标志物进行比较。在 此外，这将为评估其他双重任务的机会提供机会，这些双任务可能更敏感 整个智商范围（即，与严重ID的边界），并提供必要的试点数据以进行功率分析 未来的R01提交。最后，飞行员将提供一个可以共享和可用的丰富数据集 给其他研究人员，并允许测试与U19AG068054中项目相关的假设。