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: 10276389
• 负责人: Stacy Andersen
• 金额: $ 427.9万
• 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/10276389
• 关键词: 3-Dimensional; Aging; Alzheimer associated neurodegeneration; 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 Combinations; Drug usage; Exposure to; Functional Magnetic Resonance Imaging; Genes; Human; Impaired cognition; Lead; Life Expectancy; Measures; MicroRNAs; Microglia; Modeling; Molecular; Neurons; Neuropsychology; Organoids; Pathway interactions; Pharmaceutical Preparations; Phenotype; Plasma; Prospective Studies; RNA; RNA Sequences; Resistance; Risk; Risk Factors; Sampling; Septuagenarian; Serum; Spouses; Structure; 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; neuroimaging; neuroinflammation; neuropathology; offspring; protective factors; relating to nervous system; 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.

总体组件总结 百岁老人将与年龄有关的疾病和残疾推迟到90多岁。有一些是 尽管极度暴露于认知障碍的最强风险因素， 和AD，老化。这项研究的总体假设，题为“恢复力/抗AD， 百岁老人和后代”（RADCO）是：百岁老人的认知超级老人和他们的一些 后代具有保护性因素，赋予这种恢复力，在某些情况下，甚至是抵抗力 对抗认知能力下降和痴呆症RADCO收集了前所未有的大量样本， 前瞻性研究了百岁认知超级老人（n=495，基本上，百岁老人与 福尔斯的认知功能符合七十岁老人的标准）沿着后代（n=600）， 后代配偶（n=120），谁，通过RADCO核心，经过仔细，全面和切割， 边缘神经心理学、生物标志物、神经影像学和神经病理学表型。这些 数据被两个项目使用，其总体科学目标是衡量认知弹性 在这个例子中，了解潜在的保护生物学，并将其转化为 治疗目标认知弹性和抵抗表型项目（项目1） 通过神经影像学、血浆AD生物标志物风险和神经病理学测量恢复力， 产生了一系列恢复力的内在表型。保护因素和机制项目 （项目2）是RADCO的翻译分支;它发现基因，候选生物途径 以及与弹性内表型相关的mi-RNA调节子组，其特征在于 项目1。AD的体外模型包括皮质神经元、小胶质细胞和星形胶质细胞 使用由百岁老人认知超级老人诱导多能干细胞（iPSC）系创建的 来测试候选途径如何引起对AD的恢复。