Department of Pathology and Immunology and Department of Neurology, Washington University School of Medicine in St Louis, USA.
Department of Pathology and Immunology and Department of Neurology, Washington University School of Medicine in St Louis, USA.
Curr Opin Immunol. 2022 Aug;77:102233. doi: 10.1016/j.coi.2022.102233. Epub 2022 Jul 12.
Alzheimer's disease (AD) is the leading cause of dementia in the elderly. Although AD is primarily a neurological disorder distinguished by amyloid β plaques and intracellular neurofibrillary tangles, the immune system can impact the progression of the disease and may be targeted for therapeutic purposes. To date, most studies have focused on innate immune responses of microglia. However, emerging evidence implicates adaptive immune responses by T cells and B cells in the progression of AD. Moreover, the recent approval of an antibody that promotes amyloid β plaque clearance for AD therapy has pinpointed adaptive immunity as a fertile ground for the design of novel therapeutic approaches. Here, we highlight key studies delineating T cell and B cell responses in human AD and mouse models of AD, identify open questions on the specificity, development and impact of these responses and discuss outlooks for future studies and novel therapeutic avenues.
阿尔茨海默病(AD)是老年人痴呆症的主要病因。虽然 AD 主要是一种神经系统疾病,其特征是淀粉样β斑块和细胞内神经原纤维缠结,但免疫系统会影响疾病的进展,并且可能成为治疗的靶点。迄今为止,大多数研究都集中在小胶质细胞的固有免疫反应上。然而,新出现的证据表明 T 细胞和 B 细胞的适应性免疫反应参与了 AD 的进展。此外,最近批准了一种用于 AD 治疗的促进淀粉样β斑块清除的抗体,这一事实表明适应性免疫是设计新型治疗方法的一个有希望的领域。在这里,我们重点介绍了阐明人类 AD 和 AD 小鼠模型中 T 细胞和 B 细胞反应的关键研究,确定了这些反应的特异性、发展和影响方面的开放性问题,并讨论了未来研究和新型治疗途径的前景。