小胶质细胞
神经科学
神经病理学
生物
神经炎症
先天免疫系统
干扰素
炎症
淀粉样蛋白(真菌学)
免疫学
认知功能衰退
老年斑
Ⅰ型干扰素
阿尔茨海默病
免疫系统
疾病
医学
病理
痴呆
植物
作者
Ethan Roy,Gabriel Sean-Hang Chiu,Sanming Li,Nicholas E. Propson,Rupa S. Kanchi,Baiping Wang,Cristian Coarfa,Hui Zheng,Wei Cao
出处
期刊:Immunity
[Elsevier]
日期:2022-05-01
卷期号:55 (5): 879-894.e6
被引量:66
标识
DOI:10.1016/j.immuni.2022.03.018
摘要
Summary
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 examined their role in cognition and neuropathology relevant to AD in a murine amyloidosis model. 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 other cell types. Long-term blockade of IFN-I receptor (IFNAR) rescued both memory and synaptic deficits 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 network of AD and prompts concerted cellular states that are detrimental to memory and cognition.
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