Early cognitive decline in Down syndrome - Supplement

摘要 唐氏综合征(DS)是一种由细胞分裂错误导致额外复制的 21号染色体。结果是智力残疾，身体特征，以及几种医学上的 漏洞。此外，DS与加速衰老过程和非常高的风险有关 阿尔茨海默病(AD)。阿尔茨海默病神经病理的经典成分-淀粉样斑块和 神经原纤维缠结(NFT)-两者都受到染色体上过度表达的基因的影响 21.其中一个基因是APP，它产生淀粉样β蛋白(Aβ)前体蛋白，并且可以在 过量，会导致Aβ在大脑中有害的沉积(斑块)。其他几个基因 位于21号染色体上，包括DYRK1a，有助于Aβ沉积和tau沉积 (NFTS)以及神经炎症和胆固醇升高--所有这些都会导致AD。到目前为止， 众所周知，在30多岁的成年DS患者中，可以检测到DS的认知能力下降。S和 40‘S，部分功能减退对AD的诊断有一定的预测作用。我们认为，一些下降 可能在较早的年龄就可以检测到，特别是因为阿尔茨海默病的神经病理早在年龄之前就开始了 患有DS的患者为20年。因此，在我们的母公司R01研究中，唐氏综合症的早期认知下降 (R01HD098179)，我们研究了三年来认知、语言和行为方面的下降 15-25岁的青少年和青壮年的功能。如果在这个年龄段可以检测到衰退 随着年龄的增长，有可能开发出潜在地提高生活质量的预防性疗法 并延缓DS患者的早期衰老和AD的进展。广泛而长期的目标是 目前的补充项目是在父母研究中增加血液采集和银行。 与AD相关的血液生物标记物可能有助于区分早期衰退 这些都是健康衰老加速的症状和临床前的早期衰退症状 广告。为期一年的补充计划的第一个目标是收集和储存参与者的血液样本。 在父母研究的时间1患有唐氏综合症。所有已参加 父母研究(N=60)将被邀请在父母研究的第一时间抽血。血液将被储存起来 在加州大学戴维斯分校。目标2是从血液样本中量化生物标记物，并创建一个 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β蛋白、tau蛋白和DYRK1a 蛋白质，以及神经丝光，炎症标志物，胆固醇/血脂水平，甲状腺水平， APOE基因多态。当母体研究完成后，生物标志物数据将是 与父母研究的行为数据一起分析，以确定与以下方面相关的下降 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.