β-Amyloid aggregates found in brain plaques are viewed as triggers of cytotoxicity and neuroinflammation in Alzheimer disease (AD). However, the main β-amyloid (Aβ) species and what imbues the aggregates with such toxic potential are still not yet understood. In this issue of the JCI, Roy et al. show that Aβ complexed with nucleic acids triggers an antiviral type I interferon response in neuroglia, resulting in complement-mediated synapse elimination in AD models. These findings identify a putative endogenous immune signaling axis that drives neurodegeneration in AD and has strong implications for the development of precise therapeutic strategies.

在大脑斑块中发现的β-淀粉样蛋白聚集体被认为是阿尔茨海默病（AD）中细胞毒性和神经炎症的触发因素。然而，主要的β-淀粉样蛋白（Aβ）种类以及使聚集体具有这种潜在毒性的物质仍未被了解。在本期JCI中，Roy等人。结果表明，与核酸复合的Aβ会触发神经胶质细胞产生抗病毒I型干扰素反应，从而导致AD模型中补体介导的突触消除。这些发现确定了推定的内源性免疫信号传导轴，该轴驱动AD中的神经退行性变，并对精确治疗策略的发展具有重要意义。