PRESENCE AND ROLE OF IMMUNE MARKERS IN ALZHEIMER'S BRAIN

PI实验室的先前发现表明：1） 免疫系统的经典标志物，包括IL-2受体，NK， HLA-DP、HLA-DQ和HLA-DR在人脑中大量表达; 2)HLA-DR的表达随着年龄的增长而增加， 疾病（AD）; 3）HLA-DR免疫阳性细胞，包括 假定的星形胶质细胞、小胶质细胞和巨噬细胞，与 AD的老年斑; 4）这些细胞摄取并可能处理 AD中异常的淀粉样蛋白; 5）这些细胞具有表面 受体所必需的异常蛋白质， 活化的T细胞的抗原; 6）活化的T细胞可以是 在AD脑中发现;和7）推定的并置 具有脑胶质细胞的T细胞是抗原呈递所必需的， 被证明。 本建议体现了一种努力，以证明一个具体的 脑胶质细胞和巨噬细胞的免疫相关作用， 广泛神经退化的主要决定因素 AD的特征。 这既是一个新的和一个旧的想法-老在 大脑胶质细胞和巨噬细胞一直被认为是 参与清除AD的病理碎片，但 新的信念，他们可能这样做的免疫环境。 如果成功，拟议的实验将有助于证明 新的发病机制，并可能有重要的 这对几种其它神经系统疾病也有影响（例如， 多发性硬化症），其已经具有明确的神经免疫相关性。

Previous findings from the PI's laboratory demonstrate: 1) that classic markers of the immune system, including IL-2 receptors, NK, HLA-DP, HLA-DQ, and HLA-DR, are profusely expressed in human brain; 2) that HLA-DR expression increases with age and Alzheimer's disease (AD); 3) that HLA-DR immunopositive cells, including putative astrocytes, microglia, and macrophages, co-localize with the senile plaques of AD; 4) that such cells ingest and may process the abnormal protein amyloid in AD; 5) that such cells bear surface receptors necessary for presentation of abnormal proteins as antigens to activated T cells; 6) that activated T cells can be found in the AD brain; and 7) that the apposition of presumptive T cells with brain glia, necessary for antigen presentation, can be demonstrated. The present proposal embodies an effort to demonstrate a specific immune-related action of brain glia and macrophages as one of the primary determinants of the widespread neural degeneration characteristic of AD. This is both a new and an old idea-old in the sense that brain glia and macrophages have long been presumed to be involved in clearing away the pathologic debris of AD, but new in the belief that they may be doing so in an immune context. If successful, the proposed experiments will help demonstrate a novel pathogenetic mechanism in AD, and could have important implications as well for several other neurologic disorders (e.g., multiple sclerosis) which already have clear neuoimmune correlates.