Interleukin‐12/23 deficiency differentially affects pathology in male and female Alzheimer's disease‐like mice
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‐sp...
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| Veröffentlicht in: | EMBO reports 2020-03, Vol.21 (3), p.e48530-n/a |
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| creator | Eede, Pascale Obst, Juliane Benke, Eileen Yvon‐Durocher, Genevieve Richard, Bernhard C Gimber, Niclas Schmoranzer, Jan Böddrich, Annett Wanker, Erich E Prokop, Stefan Heppner, Frank L |
| description | 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 Aβ
1–40
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.
Synopsis
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.
Female APP23 mice show stronger amyloidosis compared with male mice.
Lack of IL‐12/IL‐23 signaling reduces Aβ plaque load in male APP23 mice and affects plasma IFNγ levels.
In female APP23 mice, deficiency in IL‐12/IL‐23 signaling reduces soluble Aβ1‐40 and modulates various brain and plasma cytokines.
Graphical Abstract
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. |
| doi_str_mv | 10.15252/embr.201948530 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_7054677</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2350093176</sourcerecordid><originalsourceid>FETCH-LOGICAL-c5130-23132c5cebe0c6cef143b2a9b7df3cbc595266dca35c5a8e435fbec96a2841f73</originalsourceid><addsrcrecordid>eNqFkctOHDEQRS0ECo9kzS6yxCJshvGj3Q8WkQgigEQUKUqk7Cy3uzxjcLsndneiziqfkG_kSzDMMCGRUFYuq869qqqL0D4lR1QwwabQ1uGIEVplpeBkA-3QLK8mnBbl5qpmjH7dRrsxXhNCRFWUL9A2Z4RwmpU7KFz6HoKD4cb621-_KZsyjhswVlvwesSNNQYC-N4q50as0k_3ES9UP-9cNxux9bhVDrDyDTbwUJ64n3OwLYQ3MekjqAjJ2tkbwK3V8BJtGeUivFq9e-jL-7PPpxeTq4_nl6cnVxMtKCcTxilnWmiogehcg6EZr5mq6qIxXNdaVILleaMVF1qoEjIuTA26yhUrM2oKvofeLn0XQ91Co9MSQTm5CLZVYZSdsvLvjrdzOeu-y4KILC_uDQ5XBqH7NkDsZWujBueUh26IknFBSJVunSf04B_0uhuCT-slqiCsTAeniZouKR26GAOY9TCUyIc85X2ecp1nUrx-usOafwwwAcdL4Id1MP7PT559ePfpqTtZimPS-RmEP1M_N9AdjS3AwA</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2370282001</pqid></control><display><type>article</type><title>Interleukin‐12/23 deficiency differentially affects pathology in male and female Alzheimer's disease‐like mice</title><source>MEDLINE</source><source>Springer Nature OA Free Journals</source><source>Access via Wiley Online Library</source><source>EZB-FREE-00999 freely available EZB journals</source><source>Wiley Online Library (Open Access Collection)</source><source>PubMed Central</source><creator>Eede, Pascale ; Obst, Juliane ; Benke, Eileen ; Yvon‐Durocher, Genevieve ; Richard, Bernhard C ; Gimber, Niclas ; Schmoranzer, Jan ; Böddrich, Annett ; Wanker, Erich E ; Prokop, Stefan ; Heppner, Frank L</creator><creatorcontrib>Eede, Pascale ; Obst, Juliane ; Benke, Eileen ; Yvon‐Durocher, Genevieve ; Richard, Bernhard C ; Gimber, Niclas ; Schmoranzer, Jan ; Böddrich, Annett ; Wanker, Erich E ; Prokop, Stefan ; Heppner, Frank L</creatorcontrib><description>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 Aβ
1–40
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.
Synopsis
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.
Female APP23 mice show stronger amyloidosis compared with male mice.
Lack of IL‐12/IL‐23 signaling reduces Aβ plaque load in male APP23 mice and affects plasma IFNγ levels.
In female APP23 mice, deficiency in IL‐12/IL‐23 signaling reduces soluble Aβ1‐40 and modulates various brain and plasma cytokines.
Graphical Abstract
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.</description><identifier>ISSN: 1469-221X</identifier><identifier>EISSN: 1469-3178</identifier><identifier>DOI: 10.15252/embr.201948530</identifier><identifier>PMID: 32003148</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>Alzheimer Disease - genetics ; Alzheimer's disease ; Amyloid ; Amyloid beta-Peptides - metabolism ; Amyloid beta-Protein Precursor - metabolism ; Amyloidogenesis ; Amyloidosis ; Animals ; Brain ; Brain - metabolism ; Cytokines ; Disease Models, Animal ; EMBO19 ; EMBO24 ; EMBO27 ; Female ; Gender ; Gender aspects ; Gender differences ; Gliosis ; IL‐12/IL‐23 ; Immune system ; Innate immunity ; Interleukin 1 ; Interleukin-12 - deficiency ; Interleukin-12 - genetics ; Interleukin-12 Subunit p40 - deficiency ; Interleukin-12 Subunit p40 - genetics ; Interleukin-23 Subunit p19 - deficiency ; Interleukin-23 Subunit p19 - genetics ; Interleukins ; Male ; Mice ; Mice, Transgenic ; Neurodegenerative diseases ; Pathogenesis ; Pathology ; Plaque, Amyloid ; Rodents ; Sex differences ; Signaling ; β‐amyloid ; γ-Interferon</subject><ispartof>EMBO reports, 2020-03, Vol.21 (3), p.e48530-n/a</ispartof><rights>The Author(s) 2020</rights><rights>2020 The Authors. Published under the terms of the CC BY 4.0 license</rights><rights>2020 The Authors. Published under the terms of the CC BY 4.0 license.</rights><rights>2020 EMBO</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5130-23132c5cebe0c6cef143b2a9b7df3cbc595266dca35c5a8e435fbec96a2841f73</citedby><cites>FETCH-LOGICAL-c5130-23132c5cebe0c6cef143b2a9b7df3cbc595266dca35c5a8e435fbec96a2841f73</cites><orcidid>0000-0002-0272-8607 ; 0000-0002-5633-2149 ; 0000-0001-9456-3063 ; 0000-0002-4482-7080 ; 0000-0001-8072-1630 ; 0000-0001-9816-8917</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7054677/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7054677/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,1417,1433,27924,27925,41120,42189,45574,45575,46409,46833,51576,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32003148$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Eede, Pascale</creatorcontrib><creatorcontrib>Obst, Juliane</creatorcontrib><creatorcontrib>Benke, Eileen</creatorcontrib><creatorcontrib>Yvon‐Durocher, Genevieve</creatorcontrib><creatorcontrib>Richard, Bernhard C</creatorcontrib><creatorcontrib>Gimber, Niclas</creatorcontrib><creatorcontrib>Schmoranzer, Jan</creatorcontrib><creatorcontrib>Böddrich, Annett</creatorcontrib><creatorcontrib>Wanker, Erich E</creatorcontrib><creatorcontrib>Prokop, Stefan</creatorcontrib><creatorcontrib>Heppner, Frank L</creatorcontrib><title>Interleukin‐12/23 deficiency differentially affects pathology in male and female Alzheimer's disease‐like mice</title><title>EMBO reports</title><addtitle>EMBO Rep</addtitle><addtitle>EMBO Rep</addtitle><description>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 Aβ
1–40
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.
Synopsis
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.
Female APP23 mice show stronger amyloidosis compared with male mice.
Lack of IL‐12/IL‐23 signaling reduces Aβ plaque load in male APP23 mice and affects plasma IFNγ levels.
In female APP23 mice, deficiency in IL‐12/IL‐23 signaling reduces soluble Aβ1‐40 and modulates various brain and plasma cytokines.
Graphical Abstract
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.</description><subject>Alzheimer Disease - genetics</subject><subject>Alzheimer's disease</subject><subject>Amyloid</subject><subject>Amyloid beta-Peptides - metabolism</subject><subject>Amyloid beta-Protein Precursor - metabolism</subject><subject>Amyloidogenesis</subject><subject>Amyloidosis</subject><subject>Animals</subject><subject>Brain</subject><subject>Brain - metabolism</subject><subject>Cytokines</subject><subject>Disease Models, Animal</subject><subject>EMBO19</subject><subject>EMBO24</subject><subject>EMBO27</subject><subject>Female</subject><subject>Gender</subject><subject>Gender aspects</subject><subject>Gender differences</subject><subject>Gliosis</subject><subject>IL‐12/IL‐23</subject><subject>Immune system</subject><subject>Innate immunity</subject><subject>Interleukin 1</subject><subject>Interleukin-12 - deficiency</subject><subject>Interleukin-12 - genetics</subject><subject>Interleukin-12 Subunit p40 - deficiency</subject><subject>Interleukin-12 Subunit p40 - genetics</subject><subject>Interleukin-23 Subunit p19 - deficiency</subject><subject>Interleukin-23 Subunit p19 - genetics</subject><subject>Interleukins</subject><subject>Male</subject><subject>Mice</subject><subject>Mice, Transgenic</subject><subject>Neurodegenerative diseases</subject><subject>Pathogenesis</subject><subject>Pathology</subject><subject>Plaque, Amyloid</subject><subject>Rodents</subject><subject>Sex differences</subject><subject>Signaling</subject><subject>β‐amyloid</subject><subject>γ-Interferon</subject><issn>1469-221X</issn><issn>1469-3178</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>24P</sourceid><sourceid>WIN</sourceid><sourceid>EIF</sourceid><recordid>eNqFkctOHDEQRS0ECo9kzS6yxCJshvGj3Q8WkQgigEQUKUqk7Cy3uzxjcLsndneiziqfkG_kSzDMMCGRUFYuq869qqqL0D4lR1QwwabQ1uGIEVplpeBkA-3QLK8mnBbl5qpmjH7dRrsxXhNCRFWUL9A2Z4RwmpU7KFz6HoKD4cb621-_KZsyjhswVlvwesSNNQYC-N4q50as0k_3ES9UP-9cNxux9bhVDrDyDTbwUJ64n3OwLYQ3MekjqAjJ2tkbwK3V8BJtGeUivFq9e-jL-7PPpxeTq4_nl6cnVxMtKCcTxilnWmiogehcg6EZr5mq6qIxXNdaVILleaMVF1qoEjIuTA26yhUrM2oKvofeLn0XQ91Co9MSQTm5CLZVYZSdsvLvjrdzOeu-y4KILC_uDQ5XBqH7NkDsZWujBueUh26IknFBSJVunSf04B_0uhuCT-slqiCsTAeniZouKR26GAOY9TCUyIc85X2ecp1nUrx-usOafwwwAcdL4Id1MP7PT559ePfpqTtZimPS-RmEP1M_N9AdjS3AwA</recordid><startdate>20200304</startdate><enddate>20200304</enddate><creator>Eede, Pascale</creator><creator>Obst, Juliane</creator><creator>Benke, Eileen</creator><creator>Yvon‐Durocher, Genevieve</creator><creator>Richard, Bernhard C</creator><creator>Gimber, Niclas</creator><creator>Schmoranzer, Jan</creator><creator>Böddrich, Annett</creator><creator>Wanker, Erich E</creator><creator>Prokop, Stefan</creator><creator>Heppner, Frank L</creator><general>Nature Publishing Group UK</general><general>Blackwell Publishing Ltd</general><general>John Wiley and Sons Inc</general><scope>C6C</scope><scope>24P</scope><scope>WIN</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QL</scope><scope>7T5</scope><scope>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>K9.</scope><scope>M7N</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-0272-8607</orcidid><orcidid>https://orcid.org/0000-0002-5633-2149</orcidid><orcidid>https://orcid.org/0000-0001-9456-3063</orcidid><orcidid>https://orcid.org/0000-0002-4482-7080</orcidid><orcidid>https://orcid.org/0000-0001-8072-1630</orcidid><orcidid>https://orcid.org/0000-0001-9816-8917</orcidid></search><sort><creationdate>20200304</creationdate><title>Interleukin‐12/23 deficiency differentially affects pathology in male and female Alzheimer's disease‐like mice</title><author>Eede, Pascale ; Obst, Juliane ; Benke, Eileen ; Yvon‐Durocher, Genevieve ; Richard, Bernhard C ; Gimber, Niclas ; Schmoranzer, Jan ; Böddrich, Annett ; Wanker, Erich E ; Prokop, Stefan ; Heppner, Frank L</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5130-23132c5cebe0c6cef143b2a9b7df3cbc595266dca35c5a8e435fbec96a2841f73</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Alzheimer Disease - genetics</topic><topic>Alzheimer's disease</topic><topic>Amyloid</topic><topic>Amyloid beta-Peptides - metabolism</topic><topic>Amyloid beta-Protein Precursor - metabolism</topic><topic>Amyloidogenesis</topic><topic>Amyloidosis</topic><topic>Animals</topic><topic>Brain</topic><topic>Brain - metabolism</topic><topic>Cytokines</topic><topic>Disease Models, Animal</topic><topic>EMBO19</topic><topic>EMBO24</topic><topic>EMBO27</topic><topic>Female</topic><topic>Gender</topic><topic>Gender aspects</topic><topic>Gender differences</topic><topic>Gliosis</topic><topic>IL‐12/IL‐23</topic><topic>Immune system</topic><topic>Innate immunity</topic><topic>Interleukin 1</topic><topic>Interleukin-12 - deficiency</topic><topic>Interleukin-12 - genetics</topic><topic>Interleukin-12 Subunit p40 - deficiency</topic><topic>Interleukin-12 Subunit p40 - genetics</topic><topic>Interleukin-23 Subunit p19 - deficiency</topic><topic>Interleukin-23 Subunit p19 - genetics</topic><topic>Interleukins</topic><topic>Male</topic><topic>Mice</topic><topic>Mice, Transgenic</topic><topic>Neurodegenerative diseases</topic><topic>Pathogenesis</topic><topic>Pathology</topic><topic>Plaque, Amyloid</topic><topic>Rodents</topic><topic>Sex differences</topic><topic>Signaling</topic><topic>β‐amyloid</topic><topic>γ-Interferon</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Eede, Pascale</creatorcontrib><creatorcontrib>Obst, Juliane</creatorcontrib><creatorcontrib>Benke, Eileen</creatorcontrib><creatorcontrib>Yvon‐Durocher, Genevieve</creatorcontrib><creatorcontrib>Richard, Bernhard C</creatorcontrib><creatorcontrib>Gimber, Niclas</creatorcontrib><creatorcontrib>Schmoranzer, Jan</creatorcontrib><creatorcontrib>Böddrich, Annett</creatorcontrib><creatorcontrib>Wanker, Erich E</creatorcontrib><creatorcontrib>Prokop, Stefan</creatorcontrib><creatorcontrib>Heppner, Frank L</creatorcontrib><collection>Springer Nature OA Free Journals</collection><collection>Wiley Online Library (Open Access Collection)</collection><collection>Wiley Online Library (Open Access Collection)</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Immunology Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>EMBO reports</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Eede, Pascale</au><au>Obst, Juliane</au><au>Benke, Eileen</au><au>Yvon‐Durocher, Genevieve</au><au>Richard, Bernhard C</au><au>Gimber, Niclas</au><au>Schmoranzer, Jan</au><au>Böddrich, Annett</au><au>Wanker, Erich E</au><au>Prokop, Stefan</au><au>Heppner, Frank L</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Interleukin‐12/23 deficiency differentially affects pathology in male and female Alzheimer's disease‐like mice</atitle><jtitle>EMBO reports</jtitle><stitle>EMBO Rep</stitle><addtitle>EMBO Rep</addtitle><date>2020-03-04</date><risdate>2020</risdate><volume>21</volume><issue>3</issue><spage>e48530</spage><epage>n/a</epage><pages>e48530-n/a</pages><issn>1469-221X</issn><eissn>1469-3178</eissn><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 Aβ
1–40
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.
Synopsis
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.
Female APP23 mice show stronger amyloidosis compared with male mice.
Lack of IL‐12/IL‐23 signaling reduces Aβ plaque load in male APP23 mice and affects plasma IFNγ levels.
In female APP23 mice, deficiency in IL‐12/IL‐23 signaling reduces soluble Aβ1‐40 and modulates various brain and plasma cytokines.
Graphical Abstract
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.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>32003148</pmid><doi>10.15252/embr.201948530</doi><tpages>18</tpages><orcidid>https://orcid.org/0000-0002-0272-8607</orcidid><orcidid>https://orcid.org/0000-0002-5633-2149</orcidid><orcidid>https://orcid.org/0000-0001-9456-3063</orcidid><orcidid>https://orcid.org/0000-0002-4482-7080</orcidid><orcidid>https://orcid.org/0000-0001-8072-1630</orcidid><orcidid>https://orcid.org/0000-0001-9816-8917</orcidid><oa>free_for_read</oa></addata></record> |
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| ispartof | EMBO reports, 2020-03, Vol.21 (3), p.e48530-n/a |
| issn | 1469-221X 1469-3178 |
| language | eng |
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| source | MEDLINE; Springer Nature OA Free Journals; Access via Wiley Online Library; EZB-FREE-00999 freely available EZB journals; Wiley Online Library (Open Access Collection); PubMed Central |
| subjects | Alzheimer Disease - genetics Alzheimer's disease Amyloid Amyloid beta-Peptides - metabolism Amyloid beta-Protein Precursor - metabolism Amyloidogenesis Amyloidosis Animals Brain Brain - metabolism Cytokines Disease Models, Animal EMBO19 EMBO24 EMBO27 Female Gender Gender aspects Gender differences Gliosis IL‐12/IL‐23 Immune system Innate immunity Interleukin 1 Interleukin-12 - deficiency Interleukin-12 - genetics Interleukin-12 Subunit p40 - deficiency Interleukin-12 Subunit p40 - genetics Interleukin-23 Subunit p19 - deficiency Interleukin-23 Subunit p19 - genetics Interleukins Male Mice Mice, Transgenic Neurodegenerative diseases Pathogenesis Pathology Plaque, Amyloid Rodents Sex differences Signaling β‐amyloid γ-Interferon |
| title | Interleukin‐12/23 deficiency differentially affects pathology in male and female Alzheimer's disease‐like mice |
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