Protective factors and mechanisms

RADCO项目2摘要 许多认知障碍和痴呆症的研究都集中在疾病机制上。 以及破坏这些活动的目标。一个令人信服的替代方法是自然地描绘 发生的保护机制。一些百岁老人在认知上仍然完好无损，尽管 极端暴露在认知障碍和AD、衰老的最强风险因素中。我们 假设这些百岁老人和他们的部分后代有保护因素 这会导致这种韧性，甚至在某些情况下，对认知能力下降的抵抗 痴呆症。在行政、表型和生物样本的支持下，以及 神经成像核心和项目1(恢复力和阻力表型)，这是 《百岁老人及其后代对阿尔茨海默病的抵抗力/恢复力》(RADCO)研究致力于 发现预防认知障碍、阿尔茨海默病和其他疾病的因素和机制 痴呆症。该项目涉及三种相关方法：遗传学(目标1)、转录学 年龄相关脑病理的分析(AIM 2)和3D人类神经胶质细胞培养模型(AIM 3)。我们的目标是1)识别抗逆性/抗逆性的遗传变异和生物学机制 在百岁认知超老年人中，2)预测认知弹性的机制并验证 可以增强人脑细胞弹性/抵抗力的候选药物，以及3)建立 百岁老人诱导多能干细胞及其衍生的3D脑细胞模型 超级老人来测试这些机制，以及发现和测试其他可能被利用的机制 用于保护性治疗。

RADCO Project 2 Summary Much of cognitive impairment and dementia research has concentrated on disease mechanisms and targets for disrupting these. A compelling alternative approach is to delineate naturally occurring mechanisms of protection. Some centenarians remain cognitively intact despite an extreme exposure to the strongest risk factor for cognitive impairment and AD, aging. We hypothesize that these centenarians and some portion of their offspring have protective factors that lead to such resilience or in some cases, even resistance against cognitive decline and dementia. With the support of the Administrative, Phenotyping and Biosamples, and Neuroimaging Cores, and Project 1 (Resilience and Resistance Phenotypes), this 2nd project of the “Resistance/Resilience to AD in Centenarians and Offspring" (RADCO) study strives to discover factors and mechanisms protective against cognitive impairment, AD and other dementias. This project entails three related approaches: genetics (Aim 1), transcriptomic analyses (Aim 2), and 3D human neural-glial culture models of age-related brain pathology (Aim 3). Our goals are to 1) identify genetic variants and biological mechanisms of resilience/resistance in centenarian cognitive superagers, 2) predict mechanisms of cognitive resilience and validate candidate drugs that can enhance the resilience/resistance in human brain cells, and 3) establish induced pluripotent stem cells (iPSCs) and iPSC-derived 3D brain cell models of the centenarian superagers to test those mechanisms as well as discover and test others that could be exploitable for protective therapeutics.