ABC-DS MOMs’ Supplement (Modification of Maternal AD risk in DS)

ABC-DS MOMs™ 补充（DS 孕产妇 AD 风险修改）

• 批准号: 10595165
• 负责人: Bradley T Christian
• 金额: $ 78.87万
• 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/10595165
• 关键词: Address; Adult; Adult Children; Age; Age of Onset; Age-Years; Alleles; Alzheimer' s Disease; Alzheimer' s disease related dementia; Alzheimer' s disease risk; Alzheimer’s disease biomarker; Amyloid beta-Protein Precursor; Biological Markers; Biology; Birth; Blood; Brain; Child; Chromosome 21; Cross-Sectional Studies; Data; Data Set; Dementia; Diagnosis; Down Syndrome; Enrollment; Family; Family history of; Fathers; Feasibility Studies; Frequencies; Funding; Future; General Population; Genes; Genetic; Glucose; Health; Individual; Intellectual functioning disability; Life Style; Modification; Mothers; Onset of illness; Parents; Participant; Persons; Pharmacological Treatment; Pilot Projects; Plasma; Population; Prevention trial; Public Health; Recording of previous events; Research; Research Personnel; Risk; Sample Size; Senile Plaques; Site; Testing; Woman; aging population; apolipoprotein E-4; base; cohort; comorbidity; dementia risk; experience; genetic risk factor; gray matter; high risk; interest; member; men; middle age; neuropathology; offspring; power analysis; pre-clinical; virtual; β-amyloid burden

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 A, which is derived from the -amyloid precursor protein; the gene for -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 MOMs’ study: Modification of Maternal AD risk in DS,” we propose to leverage the currently funded Alzheimer’s Biomarker Consortium – Down Syndrome study (ABC-DS) to pilot a project focusing on parents of adults with DS, allowing us to address important questions related to the potential impact of a range of maternal genetic factors on both maternal AD risk and AD risk to their DS offspring. We propose to conduct a cross-sectional study examining blood-based AD biomarkers (e.g., plasma Aβ1-42, NfL, ptau181, ptau217) and genetic factors among a cohort of 150 healthy middle-aged and senior men and women whose adult children with DS 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 enrolling parents of adults with DS in a biomarker study. The pilot data will be used to support the submission of a larger R01 proposal and 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A的过量生产引起的，A是源自淀粉样蛋白的蛋白质的。基因 -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。 在这项补充中，“妈妈的研究：DS中母亲AD风险的修改”，我们建议利用 目前资助的阿尔茨海默氏症生物标志物联盟 - 唐氏综合症研究（ABC-DS）试行一个项目 专注于DS成年人的父母，使我们能够解决与潜在影响有关的重要问题 DS后代的母体AD风险和AD风险的一系列母体遗传因素。我们建议 进行横断面研究，检查基于血液的AD生物标志物（例如等离子体Aβ1-42，NFL，PTAU181， PTAU217）以及150名健康中年和高级男女的遗传因素 成年DS的儿童是ABC-DS的参与者。 ABC-DS一直关注400多个 自2015年以来，成人患有DS，最近被重新资助，将此队列增加到550名个人。结果将 证明将成年人的父母参加生物标志物研究的可行性。试点数据将是 用于支持提交较大R01建议的提交，并将提供可以共享的丰富数据集和 提供给其他研究人员，并允许测试与项目相关的假设 U19AG068054。