Identifying New Immunomodulatory Targets for Alzheimers and Other Neurodegenerative Diseases

摘要 阿尔茨海默病（AD）和其他神经退行性疾病是导致死亡的主要原因 美国老年人的患病率超过650万。如AD 目前无法治愈或预防，迫切需要有效的治疗方法 针对潜在的疾病过程。治疗发展的一个主要障碍是 缺乏好的目标。虽然在病理学上很重要，但淀粉样β蛋白斑块和tau蛋白 缠结不容易被药物治疗，针对这些蛋白质的治疗的临床试验 基本上都失败了。最近的全基因组关联研究已经确定了 神经免疫细胞上越来越多的调节蛋白，特别是在 小胶质细胞和星形胶质细胞的表面，这与发展AD的风险有关。的 鉴定具有神经免疫调节活性的新蛋白质可以完全 新一代的治疗靶点，有可能治疗，延迟，甚至 预防AD和其他神经退行性疾病。

ABSTRACT Alzheimer's disease (AD) and other neurodegenerative diseases are a major cause of death and disability for older Americans, with a US prevalence of more than 6.5 million. As AD currently cannot be cured or prevented, there is an urgent need for effective treatments targeting underlying disease processes. A major roadblock in treatment development has been the lack of good targets. Although pathologically important, amyloid beta plaques and tau tangles are not easily druggable, and clinical trials of therapeutics targeting these proteins directly have largely failed. Recent genome-wide association studies have identified a link between a growing number of modulatory proteins on neuroimmune cells, particularly on the surface of microglia and astrocytes, that are linked to the risk of developing AD. The identification of new proteins with neuroimmunomodulatory activities could enable an entirely new generation of therapeutic targets with the potential to treat, delay, and possibly even prevent AD and other neurodegenerative diseases.