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.

总体汇总 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=596），百岁老人与正常 认知（n=230），后代超级老人（n=480）和后代配偶（n=144），谁，通过RADCO 核心，经过仔细，全面和尖端的神经心理学，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， 总体科学目标是衡量这一样本的认知弹性，了解 保护性生物学的基础，并将其转化为治疗靶点。认知 恢复力和抵抗力表型项目（项目1）通过神经成像测量恢复力， 血浆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 内表型保护因素和机制项目（项目2）是翻译 RADCO的一个分支;它发现基因、候选生物通路和一组miRNA调节因子 与项目1中表征的弹性内表型相关。AD的体外模型 整合了大脑皮层神经元、小胶质细胞和星形胶质细胞， 超龄诱导多能干细胞（iPSC）系用于测试以下的候选途径： 它们是如何引起抗AD的恢复力的。