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.

总体摘要 百岁老人将与年龄相关的疾病和残疾推迟到90多岁。一些人留了下来 尽管极端暴露在认知障碍的最强风险因素中，但认知能力完好无损 老年痴呆症，衰老。这项研究的总体假设，题为《AD的复原力/抵抗力》 百岁老人和后代“(RADCO)，是：百岁认知超级老人和他们的一些人 后代有保护性的因素，赋予这种韧性，甚至在某些情况下，甚至抵抗 对抗认知衰退和痴呆症。RADCO收集了前所未有的大量样本 前瞻性研究百岁老人(n=596)认知功能正常的百岁老人 认知(n=230)、子女超级老年人(n=480)和子女配偶(n=144)，他们通过RADCO 核心，经过仔细的，全面的和尖端的神经心理学，生物标志物， 神经影像和神经病理表型。这些数据由两个项目使用， 在此样本中衡量认知韧性的总体科学目标，了解 潜在的保护生物学并将其转化为治疗目标。《认知》 韧性和阻力表型项目(项目1)通过神经成像来评估韧性， 血浆AD生物标志物的风险和神经病理，因此产生一系列的弹性 内表型。保护因素和机制项目(项目2)是翻译 RADCO的ARM；它发现基因、候选生物途径和一组mi-RNA调节器 与项目1中描述的弹性内表型有关：AD的体外模型 结合从百岁老人认知中产生的皮质神经元、小胶质细胞和星形胶质细胞 SuperAger诱导的多能干细胞(IPSC)系被用来测试 它们是如何对AD产生韧性的。