1. Interleukin���12/23 deficiency differentially affects pathology in male and female Alzheimer's disease���like mice
- Author
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Niclas Gimber, Jan Schmoranzer, Eileen Benke, Erich E. Wanker, Genevieve Yvon‐Durocher, Stefan Prokop, Frank L. Heppner, Juliane Obst, Annett Böddrich, Bernhard C. Richard, and Pascale Eede
- Subjects
Male ,Pathology ,medicine.medical_treatment ,genetics [Alzheimer Disease] ,Plaque, Amyloid ,Disease ,Biochemistry ,deficiency [Interleukin-12] ,Pathogenesis ,Amyloid beta-Protein Precursor ,Mice ,0302 clinical medicine ,metabolism [Amyloid beta-Protein Precursor] ,gender ,��-amyloid ,Molecular Biology of Disease ,innate immunity ,0303 health sciences ,genetics [Interleukin-12 Subunit p40] ,β-amyloid ,Interleukin-12 Subunit p40 ,Interleukin ,Brain ,Articles ,Alzheimer's disease ,Interleukin-12 ,genetics [Interleukin-23 Subunit p19] ,Astrogliosis ,Cytokine ,Interleukin 12 ,Female ,Function and Dysfunction of the Nervous System ,600 Technik, Medizin, angewandte Wissenschaften::610 Medizin und Gesundheit::610 Medizin und Gesundheit ,medicine.medical_specialty ,deficiency [Interleukin-12 Subunit p40] ,IL‐12/IL‐23 ,b-amyloid ,Immunology ,metabolism [Amyloid beta-Peptides] ,Mice, Transgenic ,deficiency [Interleukin-23 Subunit p19] ,Article ,03 medical and health sciences ,IL-12/IL-23 ,Immune system ,Alzheimer Disease ,ddc:570 ,Genetics ,medicine ,Animals ,Molecular Biology ,030304 developmental biology ,Innate immune system ,Amyloid beta-Peptides ,business.industry ,medicine.disease ,genetics [Interleukin-12] ,Disease Models, Animal ,metabolism [Brain] ,Interleukin-23 Subunit p19 ,β‐amyloid ,business ,030217 neurology & neurosurgery ,Neuroscience - 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 Aβ plaque burden in male APP23 mice, while in female mice, a significant reduction in soluble Aβ1–40 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., Abrogating IL‐12/IL‐23 signaling ameliorates amyloidogenesis gender‐specifically in APP23 mice, indicating therapeutic potential of targeting IL‐12/IL‐23 in Alzheimer's disease and highlighting the importance of gender considerations in AD.
- Published
- 2020
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