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Interleukin‐12/23 deficiency differentially affects pathology in male and female Alzheimer's disease‐like mice
Author(s) -
Eede Pascale,
Obst Juliane,
Benke Eileen,
YvonDurocher Genevieve,
Richard Bernhard C,
Gimber Niclas,
Schmoranzer Jan,
Böddrich Annett,
Wanker Erich E,
Prokop Stefan,
Heppner Frank L
Publication year - 2020
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.15252/embr.201948530
Subject(s) - neuropathology , humanities , history , medicine , art , disease , pathology
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 APP 23 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 IL 12p40, the shared subunit of interleukin ( IL )‐12 and IL ‐23, that we previously reported to ameliorate pathology in APPPS 1 mice. IL 12p40 deficiency gender specifically reduces Aβ plaque burden in male APP 23 mice, while in female mice, a significant reduction in soluble Aβ 1–40 without changes in Aβ plaque burden is seen. Similarly, plasma and brain cytokine levels are altered differently in female versus male APP 23 mice lacking IL 12p40, 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 .