Early cognitive decline in Down syndrome - Supplement

唐氏综合症的早期认知能力下降 - 补充

• 批准号: 10403731
• 负责人: FRANCES A CONNERS
• 金额: $ 26.87万
• 依托单位: UNIVERSITY OF ALABAMA IN TUSCALOOSA
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-07-15 至 2025-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10403731
• 关键词: 20 year old; Administrative Supplement; Adolescence; Adolescent; Adolescent and Young Adult; Adult; Affect; Age; Aging; Alabama; Alzheimer' s Disease; Alzheimer' s disease diagnosis; Alzheimer' s disease risk; Alzheimer’s disease biomarker; Amyloid beta-Protein; Behavioral; Biological Markers; Biological Specimen Banks; Blood; Blood Banks; Blood specimen; Brain; California; Cell division; Cholesterol; Chromosome 21; Classification; Cognitive; Collection; Congenital chromosomal disease; Data; Data Analyses; Data Set; Dementia; Deposition; Development; Disease Progression; Down Syndrome; Enrollment; Etiology; Event; Freezing; Future; Genes; Genetic Polymorphism; Goals; Head; Impaired cognition; Individual; Institutes; Intellectual functioning disability; Intervention; Language; Libraries; Life; Light; Link; Lipids; Measures; Medical; Memory; Mental Depression; Neurofibrillary Tangles; Outcome; Parents; Participant; Plasma; Preventive; Process; Protein Precursors; Proteins; Protocols documentation; Quality of life; Reporting; Research Personnel; Sampling; Senile Plaques; Sleep Disorders; Source; Symptoms; Therapeutic; Thyroid Gland; Time; Universities; axon injury; blood-based biomarker; cognitive change; cognitive function; data collection site; data submission; emerging adult; executive function; healthy aging; high risk; improved; indexing; inflammatory marker; interest; mild cognitive impairment; neurofilament; neuroinflammation; neuropathology; overexpression; pre-clinical; skills; tau Proteins; young adult

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.

抽象的 唐氏综合症 (DS) 是由细胞分裂错误导致的额外拷贝引起的 21号染色体。结果是智力残疾、身体特征和一些医学上的残疾 此外，DS 还与加速老化过程和极高的风险有关。 阿尔茨海默病 (AD) 神经病理学的经典组成部分 - 淀粉样斑块和 神经原纤维缠结 (NFT) – 均受到染色体上过度表达基因的影响 21. 这些基因之一是 APP，它产生淀粉样β (Aβ) 前体蛋白，并且可以 丰富的 Aβ 沉积物（斑块）会导致大脑中有害的积累。 位于 21 号染色体上，包括 DYRK1A，有助于 Aβ 沉积物和 tau 沉积物的积累 (NFT) 以及神经炎症和胆固醇升高——所有这些都会导致 AD。 众所周知，在 30 多岁的患有 DS 的成年人中可以检测到 DS 的认知能力下降。 40 多岁，一些功能下降预示着后来的 AD 诊断。 可能在较早的年龄就可以检测到，特别是因为 AD 神经病理学在年龄之前就开始了 DS 患者 20 年 因此，在我们的 R01 研究中，唐氏综合症的早期认知衰退。 (R01HD098179)，我们研究了三年来认知、语言和行为方面的下降 15-25岁的青少年和年轻人的功能是否可以在这个年轻人中检测到衰退。 年龄，有可能开发出可以改善生活质量的预防性疗法 减缓 DS 患者早期衰老和 AD 的进展。 目前的补充项目是在母研究中添加血液采集和储存。 与 AD 相关的血液生物标志物可能有助于区分早期衰退 这是加速健康衰老和早期衰退的症状，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 患有唐氏综合症的所有参加研究的患有唐氏综合症的参与者。 家长研究 (N = 60) 将被邀请在家长研究的第 1 时间进行抽血 血液将被储存。 加州大学戴维斯分校的目标 2 是量化血液样本中的生物标志物并创建一个 生物标志物指数数据集。感兴趣的生物标志物包括淀粉样蛋白 β、tau 和 DYRK1A。 蛋白质；以及神经丝光、炎症标记物、胆固醇/脂质水平、甲状腺水平、 和 APOE 多态性 当亲本研究完成后，将获得生物标志物数据。 与家长研究的行为数据一起进行分析，以确定与以下相关的下降 早期进展为 AD。