Mechanistic basis of inflammation in Alzheimers Disease

阿尔茨海默病炎症的机制基础

• 批准号: 10259772
• 负责人: Amal O Amer
• 金额: $ 18.47万
• 依托单位: OHIO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-15 至 2022-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10259772
• 关键词: Alzheimer' s Disease; Alzheimer' s disease brain; Alzheimer' s disease patient; Alzheimer' s disease risk; Amyloid; Amyloid beta-Protein; Antisense Oligonucleotides; Area; Brain; CASP1 gene; CASP4 gene; Caspase; Cells; Cerebrospinal Fluid; Complex; Confusion; Cytoskeleton; Deterioration; Exhibits; Gene Proteins; Genetic Variation; Grant; Homologous Gene; Housekeeping Gene; Human; Immune; Impaired cognition; In Vitro; Individual; Infection; Inflammasome; Inflammation; Inflammatory; Inflammatory Response; Interleukin-1 beta; Label; Lipopolysaccharides; Lobe; Mediating; Memory; Microglia; Mus; Neuraxis; Neurodegenerative Disorders; Patients; Prevention; Production; Promoter Regions; Protein Precursors; Reporting; Reverse Transcriptase Polymerase Chain Reaction; Role; Sampling; Synaptic plasticity; Testing; United States National Institutes of Health; Wild Type Mouse; biobank; bisulfite sequencing; brain tissue; cytokine; genome wide methylation; high risk; in vivo; insight; learning ability; member; overexpression; prevent; receptor function; response; risk variant

Abstract Alzheimer’s disease (AD) is a progressive inflammatory neurodegenerative disorder leading to debilitating cognitive dysfunction, and is still without cure or effective prevention options. Several studies demonstrated that low grade inflammation in the brain is associated with higher risk of AD. Patients with AD exhibit an overproduction of the pro-inflammatory cytokine interleukin-1 beta (IL-1β) in the cerebrospinal fluid and brain tissue. Importantly, exaggerated IL-1β levels robustly inhibit synaptic plasticity mechanisms critical for normal memory function. In this application we will determine the function of members of the canonical and non- canonical inflammasome in relation of AD.

抽象的 阿尔茨海默病 (AD) 是一种进行性炎症性神经退行性疾病，会导致患者衰弱 多项研究表明，认知功能障碍仍然没有治愈或有效的预防方案。 大脑中的低度炎症与 AD 患者的较高风险相关。 脑脊液和大脑中促炎细胞因子白细胞介素 1 β (IL-1β) 的过量产生 重要的是，过高的 IL-1β 水平会强烈抑制对正常组织至关重要的突触可塑性机制。 在这个应用中我们将确定成员函数的规范和非内存函数。 与 AD 相关的典型炎症小体。