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

摘要 阿尔茨海默病(AD)是普通人群中导致痴呆的最常见原因， 患有阿尔茨海默病的人数正在迅速增加。随着阿尔茨海默病药物治疗的重点转向 在预防试验中，人们对具有生物标记物(如ApoE4等位基因)的个体越来越感兴趣。 这使他们患痴呆症的风险更大。其中一个特别感兴趣的群体是患有唐氏综合症(DS)的成年人， 几乎所有人都将在70岁前被诊断出患有阿尔茨海默病。几乎所有的DS患者都会出现明显的 AD神经病理学，尤其是中年时的淀粉样斑块。淀粉样斑块的早期积累是 被认为是由于A的过度生产而产生的，A是由AFP-淀粉样前体蛋白衍生的； -淀粉样前体蛋白(APP)位于21号三体染色体上。而中国人的平均年龄 在患有DS的成年人中发展为AD大约为53岁，年龄有相当大的变异性 发病年龄从40岁以前到70岁以上不等。因此，其他因素，如遗传、生活方式和 并存的健康问题可能是个体AD发病年龄的原因。 在这份名为《母亲研究：DS中母亲AD风险的修改》的补充资料中，我们建议利用 目前资助的阿尔茨海默氏症生物标记物联合唐氏综合症研究(ABC-DS)用于一项试点项目 重点关注患有DS的成年人的父母，使我们能够解决与潜在影响相关的重要问题 一系列母体遗传因素对母体AD风险和其DS后代AD风险的影响。我们建议 进行一项横断面研究，检查基于血液的AD生物标志物(例如，血浆Aβ1-42，nfl，ptau181， 在150名健康的中老年男性和女性的队列中，他们的 患有DS的成年儿童是ABC-DS的参与者。ABC-DS已经跟踪了400多个 自2015年以来患有DS的成年人，最近得到了重新资助，将这一队列增加到550人。结果将 论证将成年DS患者的父母纳入生物标记物研究的可行性。试点数据将是 用于支持提交更大的R01建议书，并将提供丰富的数据集，可共享和 提供给其他研究人员，并允许测试与以下项目相关的假设 U19AG068054。

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.