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: 10689330
• 负责人: Stacy Andersen
• 金额: $ 434.51万
• 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/10689330
• 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; 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; 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 Component 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=495, essentially, centenarians with cognitive function that falls within the norms of septuagenarians) along with offspring (n=600) and offspring spouses (n=120), 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.

总体组件摘要 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 前瞻性地研究了百岁认知超级老人(n=495，本质上是百岁老人，有 认知功能属于七旬老人的正常范围)以及后代(n=600)和 子女配偶(n=120)，通过RADCO核心，接受仔细、全面和切割 边缘神经心理学，生物标记物，神经影像和神经病理表型。这些 两个项目使用了数据，总体的科学目标是评估认知韧性 在本示例中，了解潜在的保护生物学并将其转化为 治疗靶点。认知韧性和阻力表型项目(项目1) 通过神经成像、血浆AD生物标记物风险和神经病理学来衡量韧性，因此 产生一系列弹性内表型。保护因素与机制方案 (项目2)是RADCO的翻译部门；它发现基因，候选生物途径 和与弹性内表型相关的一组mi-RNA调节器，其特征在于 项目1.阿尔茨海默病体外模型包括皮质神经元、小胶质细胞和星形胶质细胞 使用由百岁认知超老诱导的多能干细胞(IPSC)系创造的 以测试候选途径如何导致对AD的弹性。