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This is especially relevant in view of recent advances in anti\u2010A\u03b2 therapies for Alzheimer's disease (AD). Here, it is shown that partial hepatic loss of A\u03b2 in transgenic AD mice immunized with A\u03b2 antibody 3D6 and its absence in amyloid precursor protein (APP) knockout mice (APP\u2010KO), as well as in human liver spheroids with APP knockdown upregulates classical hallmarks of fibrosis, smooth muscle alpha\u2010actin, and collagen type I. A\u03b2 absence in APP\u2010KO and deficiency in immunized mice lead to strong activation of transforming growth factor\u2010\u03b2 (TGF\u03b2), alpha secretases, NOTCH pathway, inflammation, decreased permeability of liver sinusoids, and epithelial\u2010mesenchymal transition. Inversely, increased systemic and intrahepatic levels of A\u03b242 in transgenic AD mice and neprilysin inhibitor LBQ657\u2010treated wild\u2010type mice protect the liver against carbon tetrachloride (CCl<jats:sub>4<\/jats:sub>)\u2010induced injury. Transcriptomic analysis of CCl<jats:sub>4<\/jats:sub>\u2010treated transgenic AD mouse livers uncovers the regulatory effects of A\u03b242 on mitochondrial function, lipid metabolism, and its onco\u2010suppressive effects accompanied by reduced synthesis of extracellular matrix proteins. Combined, these data reveal A\u03b2 as an indispensable regulator of cell\u2013cell interactions in healthy liver and a powerful protector against liver fibrosis.<\/jats:p>","DOI":"10.1002\/advs.202307734","type":"journal-article","created":{"date-parts":[[2024,3,2]],"date-time":"2024-03-02T14:34:42Z","timestamp":1709390082000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Consequences of Amyloid\u2010\u03b2 Deficiency for the Liver"],"prefix":"10.1002","volume":"11","author":[{"given":"Gayane Hrachia","family":"Buniatian","sequence":"first","affiliation":[{"name":"Department of Clinical Pharmacology University Hospital of Tuebingen  Auf der Morgenstelle 8 72076 Tuebingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ute","family":"Schwinghammer","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology University Hospital of Tuebingen  Auf der Morgenstelle 8 72076 Tuebingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roman","family":"Tremmel","sequence":"additional","affiliation":[{"name":"Dr. Margarete Fischer\u2010Bosch Institute of Clinical Pharmacology  Auerbachstr. 112 70376 Stuttgart Germany"},{"name":"University of Tuebingen  72074 Tuebingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Holger","family":"Cynis","sequence":"additional","affiliation":[{"name":"Department of Drug Design and Target Validation Fraunhofer Institute for Cell Therapy and Immunology  Weinbergweg 22 06120 Halle (Saale) Germany"},{"name":"Junior Research Group, Immunomodulation in Pathophysiological Processes Faculty of Medicine Martin\u2010Luther\u2010University Halle\u2010Wittenberg  Weinbergweg 22 06120 Halle (Saale) Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas S.","family":"Weiss","sequence":"additional","affiliation":[{"name":"Children's University Hospital (KUNO) University Hospital Regensburg  Franz\u2010Josef\u2010Strauss\u2010Allee 11 93053 Regensburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ralf","family":"Weiskirchen","sequence":"additional","affiliation":[{"name":"Institute of Molecular Pathobiochemistry Experimental Gene Therapy and Clinical Chemistry RWTH University Hospital Aachen  Pauwelsstr. 30 52074 Aachen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Volker M.","family":"Lauschke","sequence":"additional","affiliation":[{"name":"Dr. Margarete Fischer\u2010Bosch Institute of Clinical Pharmacology  Auerbachstr. 112 70376 Stuttgart Germany"},{"name":"University of Tuebingen  72074 Tuebingen Germany"},{"name":"Department of Physiology and Pharmacology Karolinska Institute  Stockholm 171 77 Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonia","family":"Youhanna","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology Karolinska Institute  Stockholm 171 77 Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isbaal","family":"Ramos","sequence":"additional","affiliation":[{"name":"Innovative Technologies in Biological Systems SL (INNOPROT)  Bizkaia Derio 48160 Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Valcarcel","sequence":"additional","affiliation":[{"name":"Innovative Technologies in Biological Systems SL (INNOPROT)  Bizkaia Derio 48160 Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Torgom","family":"Seferyan","sequence":"additional","affiliation":[{"name":"H. Buniatian Institute of Biochemistry National Academy of Sciences of the Republic of Armenia (NAS RA)  5\/1 Paruir Sevak St. Yerevan 0014 Armenia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jens\u2010Ulrich","family":"Rahfeld","sequence":"additional","affiliation":[{"name":"Department of Drug Design and Target Validation Fraunhofer Institute for Cell Therapy and Immunology  Weinbergweg 22 06120 Halle (Saale) Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vera","family":"Rieckmann","sequence":"additional","affiliation":[{"name":"Department of Drug Design and Target Validation Fraunhofer Institute for Cell Therapy and Immunology  Weinbergweg 22 06120 Halle (Saale) Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathrin","family":"Klein","sequence":"additional","affiliation":[{"name":"Dr. Margarete Fischer\u2010Bosch Institute of Clinical Pharmacology  Auerbachstr. 112 70376 Stuttgart Germany"},{"name":"University of Tuebingen  72074 Tuebingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marine","family":"Buadze","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology University Hospital of Tuebingen  Auf der Morgenstelle 8 72076 Tuebingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victoria","family":"Weber","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology University Hospital of Tuebingen  Auf der Morgenstelle 8 72076 Tuebingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentina","family":"Kolak","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology University Hospital of Tuebingen  Auf der Morgenstelle 8 72076 Tuebingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rolf","family":"Gebhardt","sequence":"additional","affiliation":[{"name":"Rudolf\u2010Sch\u00f6nheimer Institute of Biochemistry Faculty of Medicine University of Leipzig  Johannisstra\u00dfe 30 04103 Leipzig Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott L.","family":"Friedman","sequence":"additional","affiliation":[{"name":"Division of Liver Diseases Icahn School of Medicine at Mount Sinai  1425 Madison Ave New York NY 10029 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulrike C.","family":"M\u00fcller","sequence":"additional","affiliation":[{"name":"Institute for Pharmacy and Molecular Biotechnology IPMB Department of Functional Genomics University of Heidelberg  Im Neuenheimer Feld 364 69120 Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias","family":"Schwab","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology University Hospital of Tuebingen  Auf der Morgenstelle 8 72076 Tuebingen Germany"},{"name":"Dr. Margarete Fischer\u2010Bosch Institute of Clinical Pharmacology  Auerbachstr. 112 70376 Stuttgart Germany"},{"name":"Departments of Biochemistry and Clinical Pharmacology and Neuroscience Laboratory Yerevan State Medical University  2\u2010 Koryun St Yerevan 0025 Armenia"},{"name":"Cluster of Excellence iFIT (EXC2180) \u201cImage\u2010guided and Functionally Instructed Tumor Therapies\u201d University of T\u00fcbingen  72076 T\u00fcbingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4130-8477","authenticated-orcid":false,"given":"Lusine","family":"Danielyan","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology University Hospital of Tuebingen  Auf der Morgenstelle 8 72076 Tuebingen Germany"},{"name":"Departments of Biochemistry and Clinical Pharmacology and Neuroscience Laboratory Yerevan State Medical University  2\u2010 Koryun St Yerevan 0025 Armenia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,3,2]]},"reference":[{"key":"e_1_2_9_1_1","doi-asserted-by":"crossref","first-page":"146","DOI":"10.14283\/jpad.2020.24","volume":"7","author":"Aisen P. 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