Early cognitive decline in Down syndrome - Supplement

摘要 唐氏综合症（DS）是一种由细胞分裂错误引起的疾病， 21号染色体。结果是智力残疾，身体特征，和几个医疗 漏洞此外，DS与加速老化过程相关， 阿尔茨海默病（AD）。AD神经病理学的经典组成部分-淀粉样斑块和 神经纤维缠结（NFT）-都受到染色体上过表达基因的影响， 21.其中一个基因是APP，它产生淀粉样β（A β）前体蛋白， 过量的A β会导致大脑中有害的A β沉积物（斑块）。其他一些基因， 位于21号染色体上，包括DYRK1A，有助于A β沉积和tau沉积的积累 （NFT）以及神经炎症和胆固醇升高-所有这些都有助于AD。到目前为止， 已知DS的认知能力下降可以在30多岁的DS成年人中检测到， 40年代，和一些下降的功能是预测以后的AD诊断。我们认为有些下降 可能在较早的年龄就可以检测到，特别是因为AD神经病理学早在年龄之前就开始了 20年的时间里，那些与DS。因此，在我们的R01研究中，唐氏综合征的早期认知下降 （R01HD098179），我们检查了三年来认知、语言和行为的下降情况。 在青少年和年轻人，年龄15 - 25岁的功能。如果在这么年轻的时候就能检测到衰退 因此，有可能开发出预防性治疗方法，从而有可能改善生活质量。 并减缓DS患者的早期衰老和AD的进展。广泛的，长期的目标 目前的补充项目是在母研究中增加采血和建库。 与AD相关的基于血液的生物标志物可能有助于区分早期衰退 这是加速健康衰老的症状，而早期衰退是临床前的症状， ad.为期一年的补充项目的目标1是收集和储存参与者的血液样本 在母研究的时间1患有唐氏综合征。所有DS受试者， 母研究（N = 60）将受邀在母研究的时间点1进行采血。血液将被储存起来 在加州戴维斯大学。目的2是从血液样品中定量生物标志物，并建立一个 生物标志物指数的数据集。感兴趣的生物标志物包括淀粉样蛋白β、tau和DYRK1A 蛋白质;以及神经丝轻，炎症标志物，胆固醇/脂质水平，甲状腺水平， APOE多态性。当母研究完成时，生物标志物数据将 沿着来自母研究的行为数据进行分析，以确定与以下因素相关的下降： 早期进展为AD。

ABSTRACT Down syndrome (DS) is a caused by an error in cell division resulting in an extra copy of chromosome 21. The outcome is intellectual disability, physical features, and several medical vulnerabilities. Further, DS is associated with accelerated aging processes and very high risk for Alzheimer’s disease (AD). The classic components of AD neuropathology - amyloid plaques and neurofibrillary tangles (NFTs) – are both affected by overexpressed genes that are on chromosome 21. One of these genes is APP, which produces amyloid beta (Aβ) precursor protein and, can, in abundance, result in harmful buildup of Aβ deposits (plaques) in the brain. Several other genes that are on chromosome 21, including DYRK1A, contribute to buildup of Aβ deposits and tau deposits (NFTs) as well as neuroinflammation and elevated cholesterol - all of which contribute to AD. To date, it is known that cognitive decline in DS can be detected in adults with DS who are in their 30’s and 40’s, and some declining functions are predictive of later AD diagnosis. We argue that some declines may be detectable at an earlier age, especially because AD neuropathology begins well before age 20 years in those with DS. Thus, in our parent R01 study, Early Cognitive Decline in Down Syndrome (R01HD098179), we examine decline over three years in cognitive, language, and behavioral functions in adolescents and young adults, age 15-25 years. If decline can be detected at this young age, it may be possible to develop preventive therapeutics that can potentially improve quality of life and slow the progression of early aging and AD in individuals with DS. The broad, long-term goal of the present supplement project is to add blood collection and banking to the parent study. Blood-based biomarkers that are associated with AD may help distinguish between early declines that are symptoms of accelerated healthy aging and early declines that are symptoms of pre-clinical AD. Aim 1 of the 1-year supplement project is to collect and bank blood samples from participants with Down syndrome at Time 1 of the parent study. All participants with DS who are enrolled in the parent study (N = 60) will be invited for blood draw at Time 1 of the parent study. Blood will be banked at University of California Davis. Aim 2 is to quantify biomarkers from the blood samples and create a dataset of biomarker indices. The biomarkers of interest include amyloid beta, tau, and DYRK1A protein; as well as Neurofilament Light, inflammatory markers, cholesterol/lipid levels, thyroid levels, and APOE polymorphisms. When the parent study has been completed, the biomarker data will be analyzed along with the behavioral data from the parent study to identify declines that are related to early progression to AD.