The neuroinflammatory response is considered a crucial event in the pathology of Alzheimer's disease (AD). Neurotoxic amyloid β (Aβ) oligomers activate neuronal glial cells, leading to the elevated generation of a large variety of inflammatory factors. Therefore, the regulation of interleukin-1 receptor (IL-1R) activity is believed to be a potential target for AD therapy. However, previous evidence of the role of IL-1R in AD-related neuroinflammation is ambiguous. To reveal the exact role of IL-1R in AD and related inflammatory reactions, we generated IL-1R-/- AD mice. Based on the Morris water maze results, 4-month-old IL-1R-/- AD mice showed better learning and memory ability than that of AD mice. However, IL-1R-/- had little influence on amyloid precursor protein proteolysis, while IL-1R-/- increased ADAM17 expression level. Surprisingly, IL-1R-/- even enhanced glial activation. IL-1R-/- indeed attenuated inflammatory cytokine secretion, especially that of cytokins associated with M1 polarization, while it led to increased levels of some cytokins associated with M2 polarization. Finally, we found that IL-1R-/- reduced the phagocytic ability of microglia. Taken together, these results suggest that IL-1R deficiency may alleviate cognitive deficits in AD mice in a manner that is partially dependent on ADAM17 regulation and microglia M2 repolarization.
Keywords: Alzheimer’s disease (AD); Amyloid β (Aβ) peptide; Interleukin 1 receptor (IL-1R); Neuroinflammation.
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