Resilience/Resistance to Alzheimer's Disease in Centenarians and Offspring (RADCO)

百岁老人及其后代对阿尔茨海默病的抵抗力/抵抗力 (RADCO)

• 批准号: 10713947
• 负责人: Stacy Andersen
• 金额: $ 45.83万
• 依托单位: BOSTON UNIVERSITY MEDICAL CAMPUS
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-30 至 2026-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10713947
• 关键词: 3-Dimensional; Aging; Alzheimer' s Disease; Alzheimer' s disease model; Alzheimer' s disease pathology; Area; Astrocytes; Biological; Biological Assay; Biological Markers; Biology; Blood; Brain; Brain Pathology; Cell Line; Cellular Assay; Centenarian; Cognition; Cognitive; Data; Dementia; Development; Disease; Drug usage; Exposure to; Functional Magnetic Resonance Imaging; Genes; Human; Impaired cognition; Life Expectancy; Measures; MicroRNAs; Microglia; Modeling; Nerve Degeneration; Neurons; Neuropsychology; Organoids; Pathway interactions; Pharmaceutical Preparations; Phenotype; Plasma; Prospective Studies; RNA Sequences; Resistance; Risk; Risk Factors; Sampling; Septuagenarian; Serum; Spouses; Testing; Therapeutic; Tissues; Translating; Translations; Work; age related; arm; blood-brain barrier disruption; circulating biomarkers; cognitive function; cognitive testing; disability; drug candidate; endophenotype; exome; falls; gene discovery; genetic variant; in vitro Model; indexing; induced pluripotent stem cell; microRNA biomarkers; molecular resilience; neural; neuroimaging; neuroinflammation; neuropathology; offspring; promote resilience; protective factors; protective pathway; resilience; sex; therapeutic target; translational study

Overall Summary Centenarians delay age-related diseases and disabilities into their mid-nineties. Some remain cognitively intact despite extreme exposure to the strongest risk factor for cognitive impairment and AD, aging. The overall hypothesis of this study, titled “Resilience/Resistance to AD in centenarians and Offspring” (RADCO), is: centenarian cognitive superagers and some of their offspring have protective factors that confer such resilience or in some cases, even resistance against cognitive decline and dementia. RADCO assembles an unprecedentedly large sample of prospectively studied centenarian cognitive superagers (n=596), centenarians with normal cognition (n=230), offspring superagers (n=480) and offspring spouses (n=144), who, via RADCO cores, undergo careful, comprehensive and cutting edge neuropsychological, biomarker, neuroimaging and neuropathological phenotyping. These data are used by two projects with the overall scientific objective of gauging cognitive resilience in this sample, understanding the underlying protective biology and translating that into therapeutic targets. The Cognitive Resilience and Resistance Phenotypes Project (Project 1) gauges resilience by neuroimaging, plasma AD biomarkers risk and neuropathology and therefore generates a range of resilience endophenotypes. The Protective Factors and Mechanisms Project (Project 2) is the translation arm of RADCO; it discovers genes, candidate biological pathways and sets of mi-RNA regulators associated with the resilience endophenotypes characterized in Project 1. In-vitro models of AD incorporate cortical neurons, microglial cells and astrocytes created from centenarian cognitive superager induced pluripotent stem cell (iPSC) lines are used to test the candidate pathways for how they cause resilience against AD.

总结 百岁老人将与年龄有关的疾病和疾病推迟到九十年代中期。有些仍然存在 认知完整的目的地极端暴露于认知障碍的强风险因素 和广告，老化。这项研究的总体假设为“弹性/抵抗AD中的抗性 百岁老人和后代”（Radco），是：一百岁的认知超级词及其一些 后代具有受保护的因素，可以使这种弹性或在某些情况下，甚至抵抗 Radco组装了前所未有的大型样本 前瞻性研究的一百年认知超级名字（n = 596），一百岁的人正常 认知（n = 230），后代超级代表（n = 480）和后代配偶（n = 144），他通过radco 核心经过仔细，全面和最前沿的神经心理学，生物标志物， 神经影像学和神经病理学表型。这些数据由两个项目使用 在此样本中衡量认知弹性的总体科学目标，了解 保护性生物学的基础并将其转化为治疗靶标。认知 弹性和抗性表型项目（项目1）通过神经影像学得出弹性， 等离子体AD生物标志物风险和神经病理学，因此产生了一系列的弹性 内型型。保护因素和机制项目（项目2）是翻译 Radco的手臂；它发现基因，候选生物学途径和MI-RNA调节剂集 与项目1中特征的弹性内表型有关。 结合了由百年认知产生的皮质神经元，小胶质细胞和星形胶质细胞 Superager诱导的多能干细胞（IPSC）线用于测试候选途径的途径 它们如何引起对AD的弹性。