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Interleukin-12/23 deficiency differentially affects pathology in male and female Alzheimer's disease-like mice

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Item Type:Article
Title:Interleukin-12/23 deficiency differentially affects pathology in male and female Alzheimer's disease-like mice
Creators Name:Eede, P. and Obst, J. and Benke, E. and Yvon-Durocher, G. and Richard, B.C. and Gimber, N. and Schmoranzer, J. and Böddrich, A. and Wanker, E.E. and Prokop, S. and Heppner, F.L.
Abstract:Pathological aggregation of amyloid-β (Aβ) is a main hallmark of Alzheimer's disease (AD). Recent genetic association studies have linked innate immune system actions to AD development, and current evidence suggests profound gender differences in AD pathogenesis. Here, we characterise gender-specific pathologies in the APP23 AD-like mouse model and find that female mice show stronger amyloidosis and astrogliosis compared with male mice. We tested the gender-specific effect of lack of IL12p40, the shared subunit of interleukin (IL)-12 and IL-23, that we previously reported to ameliorate pathology in APPPS1 mice. IL12p40 deficiency gender specifically reduces A plaque burden in male APP23 mice, while in female mice, a significant reduction in soluble Aβ without changes in Aβ plaque burden is seen. Similarly, plasma and brain cytokine levels are altered differently in female versus male APP23 mice lacking IL12p40, while glial properties are unchanged. These data corroborate the therapeutic potential of targeting IL-12/IL-23 signalling in AD, but also highlight the importance of gender considerations when studying the role of the immune system and AD.
Keywords:Alzheimer’s Disease, Gender, IL-12/IL-23, Innate Immunity, β-Amyloid, Animals, Mice
Source:EMBO Reports
Publisher:EMBO Press / Wiley
Page Range:e48530
Date:4 March 2020
Official Publication:https://doi.org/10.15252/embr.201948530
PubMed:View item in PubMed

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