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）是由细胞分裂错误引起的，导致额外的副本 染色体21。结果是智力障碍，身体特征和几种医学 漏洞。此外，DS与加速的衰老过程有关，并且很高的风险 阿尔茨海默氏病（AD）。 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（NFTS） - 都受染色体上过表达的基因的影响 21。这些基因之一是App，它产生淀粉样蛋白β（Aβ）前体蛋白，并且可以在 抽象会导致大脑中Aβ沉积物（斑块）的有害积累。其他几个基因 在包括DYRK1A在内的21号染色体上，有助于堆积Aβ沉积物和TAU沉积物 （NFTS）以及神经炎症和胆固醇升高 - 所有这些都会促进AD。迄今为止， 众所周知，DS的认知能力下降可以在30多岁的成年人中检测到 40年代，一些功能下降的功能可预测以后的AD诊断。我们认为有些下降 可能在更早的年龄可以检测到，尤其是因为AD神经病理学在年龄之前开始 患有DS的人20年。在我们的父母R01研究中，唐氏综合症的早期认知能力下降 （R01HD098179），我们在认知，语言和行为方面检查了三年的下降 青少年和年轻人的职能，年龄15-25岁。如果在这个年轻人可以检测到下降的话 年龄，可能有可能开发有可能改善生活质量的预防疗法 并减慢DS个体早期衰老和AD的进展。广泛的长期目标 目前的补充项目是为父母的研究增加血液收集和银行业。 与AD相关的血液基本标志物可能有助于区分早期下降 这是加速健康衰老和早期下降的症状，这是临床前的症状 广告。为期1年补充项目的目标1是从参与者那里收集和银行血液样本 在父母研究的时间1​​中，有唐氏综合症。所有参加DS的参与者 父母研究（n = 60）将在父母研究的时间1​​中邀请抽血。鲜血将被存放 在加利福尼亚大学戴维斯分校。目标2是从血液样本中量化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;以及神经丝的光，炎症标记，胆固醇/脂质水平，甲状腺水平，甲状腺水平， 和ApoE多态性。父母研究完成后，生物标志物数据将是 与父母研究的行为数据一起分析，以识别与 早期发展为AD。