美国德克萨斯大学休斯顿健康科学中心Wei Cao团队发现，小胶质细胞和神经细胞中的I型干扰素信号协同作用促进与淀粉样β斑块有关的记忆障碍。相关论文于2022年4月19日在线发表于国际学术期刊《免疫》。

研究人员揭示了全脑细胞对I型干扰素（IFN-I）的反应，这是一种由淀粉样β斑块异常激发的先天免疫细胞因子，并研究了它们在小鼠淀粉样变模型中认知和与阿尔茨海默病（AD）相关的神经病理学中的作用。通过使用命运映射报告系统来追踪细胞对IFN-I的反应，研究人员在小胶质细胞和其他细胞类型中检测到强大的、依赖Aβ病理的IFN-I激活。

长期阻断IFN-I受体（IFNAR）可以挽救记忆和突触缺陷，并导致小胶质细胞、炎症和神经元病理学的减少。小胶质细胞特异性的Ifnar1缺失通过选择性吞噬减弱了突触后终端的损失，而神经Ifnar1缺失则恢复了突触前终端并减少了斑块积累。

总的来说，IFN-I信号代表了AD神经炎症网络中的一个关键模块，并促使细胞协同工作，这对记忆和认知是有害的。

据了解，驱动AD的记忆和认知障碍的主要信号仍然难以确定。

附：英文原文

Title: Concerted type I interferon signaling in microglia and neural cells promotes memory impairment associated with amyloid β plaques

Author: Ethan R. Roy, Gabriel Chiu, Sanming Li, Nicholas E. Propson, Rupa Kanchi, Baiping Wang, Cristian Coarfa, Hui Zheng, Wei Cao

Issue&Volume: 2022-04-19

Abstract: The principal signals that drive memory and cognitive impairment in Alzheimer’s disease(AD) remain elusive. Here, we revealed brain-wide cellular reactions to type I interferon(IFN-I), an innate immune cytokine aberrantly elicited by amyloid β plaques, and examinedtheir role in cognition and neuropathology relevant to AD in a murine amyloidosismodel. Using a fate-mapping reporter system to track cellular responses to IFN-I,we detected robust, Aβ-pathology-dependent IFN-I activation in microglia and othercell types. Long-term blockade of IFN-I receptor (IFNAR) rescued both memory and synapticdeficits and resulted in reduced microgliosis, inflammation, and neuritic pathology.Microglia-specific Ifnar1 deletion attenuated the loss of post-synaptic terminals by selective engulfment,whereas neural Ifnar1 deletion restored pre-synaptic terminals and decreased plaque accumulation. Overall,IFN-I signaling represents a critical module within the neuroinflammatory networkof AD and prompts concerted cellular states that are detrimental to memory and cognition.

DOI: 10.1016/j.immuni.2022.03.018

Source: https://www.cell.com/immunity/fulltext/S1074-7613(22)00141-8