研究小组引入在星形胶质细胞中表达的抗淀粉样蛋白嵌合抗原受体（CAR-A）并在体外验证其功能。课题组研究人员发现两种CAR-A设计可以减少斑块形成后的淀粉样蛋白和相关病理，并防止体内早期斑块沉积。单核RNA测序显示，CAR-A治疗诱导了淀粉样蛋白病理的独特胶质反应，涉及星形胶质细胞和小胶质细胞的协调活动。每种结构都能在星形胶质细胞或小胶质细胞中引起独特的受体特异性作用。总之，这些发现支持了CAR-A作为AD疾病改善策略的治疗潜力。
研究人员表示，阿尔茨海默病（AD）是痴呆症的主要症状，其特征是进行性淀粉样蛋白积累，随后是tau介导的神经变性。尽管抗淀粉样蛋白免疫疗法取得了进展，但重要的局限性仍然存在，这突出了对新的治疗策略的需求。
附：英文原文
Title: Targeting amyloid-β pathology by chimeric antigen receptor astrocyte (CAR-A) therapy
Author: Yun Chen, Yizhou Liu, Khai Nguyen, Junjie Wu, Sihui Song, Kent Lin, Patrick F. Rodrigues, Siling Du, Charles Zhou, Kyle Xiong, Megan Bosch, Peter Bor-Chian Lin, Darya Khantakova, Shitong Wu, May Wu, Carla Yuede, David M. Holtzman, Marco Colonna
Issue&Volume: 2026-03-05
Abstract: Alzheimer’s disease (AD) is the leading cause of dementia and is characterized by progressive amyloid accumulation followed by tau-mediated neurodegeneration. Despite advances in anti-amyloid immunotherapies, important limitations remain, highlighting the need for new therapeutic strategies. Here, we introduce anti-amyloid chimeric antigen receptors expressed in astrocytes (CAR-A) and validate their function in vitro. We show that two CAR-A designs reduce amyloid and associated pathology after plaque formation and prevent early plaque deposition in vivo. Single-nucleus RNA sequencing shows that CAR-A treatment induces a distinct glial response to amyloid pathology involving coordinated activity of astrocytes and microglia. Each construct additionally elicits distinctive, receptor-specific effects in astrocytes or microglia. Together, these findings support the therapeutic potential of CAR-A as a disease-modifying strategy for AD.
DOI: ads3972
Source: https://www.science.org/doi/10.1126/science.ads3972