Language
English
Publication Date
5-10-2022
Journal
Immunity
DOI
10.1016/j.immuni.2022.03.018
PMID
35443157
PMCID
PMC9109419
PubMedCentral® Posted Date
5-10-2023
PubMedCentral® Full Text Version
Author MSS
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 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.
Keywords
Alzheimer Disease, Amyloid beta-Peptides, Amyloid beta-Protein Precursor, Animals, Disease Models, Animal, Immunity, Innate, Interferon Type I, Memory Disorders, Mice, Mice, Transgenic, Microglia, Plaque, Amyloid, interferon, memory impairment, neuroinflammation, synapse, microglia, Alzheimer’s disease
Published Open-Access
yes
Recommended Citation
Roy, Ethan R; Chiu, Gabriel; Li, Sanming; et al., "Concerted Type I Interferon Signaling in Microglia and Neural Cells Promotes Memory Impairment Associated With Amyloid β Plaques" (2022). Faculty and Staff Publications. 1918.
https://digitalcommons.library.tmc.edu/baylor_docs/1918
Graphical Abstract
Included in
Biological Phenomena, Cell Phenomena, and Immunity Commons, Life Sciences Commons, Medical Cell Biology Commons, Medical Microbiology Commons, Medical Molecular Biology Commons, Medical Specialties Commons