Buniatian, Gayane Hrachia and Schwinghammer, Ute and Tremmel, Roman and Cynis, Holger and Weiss, Thomas S. and Weiskirchen, Ralf and Lauschke, Volker M. and Youhanna, Sonia and Ramos, Isbaal and Valcarcel, Maria and Seferyan, Torgom and Rahfeld, Jens-Ulrich and Rieckmann, Vera and Klein, Kathrin and Buadze, Marine and Weber, Victoria and Kolak, Valentina and Gebhardt, Rolf and Friedman, Scott L. and Mueller, Ulrike C. and Schwab, Matthias and Danielyan, Lusine (2024) Consequences of Amyloid-β Deficiency for the Liver. ADVANCED SCIENCE, 11 (18). ISSN , 2198-3844
Full text not available from this repository. (Request a copy)Abstract
The hepatic content of amyloid beta (A beta) decreases drastically in human and rodent cirrhosis highlighting the importance of understanding the consequences of A beta deficiency in the liver. This is especially relevant in view of recent advances in anti-A beta therapies for Alzheimer's disease (AD). Here, it is shown that partial hepatic loss of A beta in transgenic AD mice immunized with A beta antibody 3D6 and its absence in amyloid precursor protein (APP) knockout mice (APP-KO), as well as in human liver spheroids with APP knockdown upregulates classical hallmarks of fibrosis, smooth muscle alpha-actin, and collagen type I. A beta absence in APP-KO and deficiency in immunized mice lead to strong activation of transforming growth factor-beta (TGF beta), alpha secretases, NOTCH pathway, inflammation, decreased permeability of liver sinusoids, and epithelial-mesenchymal transition. Inversely, increased systemic and intrahepatic levels of A beta 42 in transgenic AD mice and neprilysin inhibitor LBQ657-treated wild-type mice protect the liver against carbon tetrachloride (CCl4)-induced injury. Transcriptomic analysis of CCl4-treated transgenic AD mouse livers uncovers the regulatory effects of A beta 42 on mitochondrial function, lipid metabolism, and its onco-suppressive effects accompanied by reduced synthesis of extracellular matrix proteins. Combined, these data reveal A beta as an indispensable regulator of cell-cell interactions in healthy liver and a powerful protector against liver fibrosis.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | FIBRILLARY ACIDIC PROTEIN; HEPATIC STELLATE CELLS; ALZHEIMERS-DISEASE; TRANSGENIC MICE; TGF-BETA; A-BETA; ENDOTHELIAL-CELLS; INTERFERON-GAMMA; DOWN-REGULATION; ACTIVATION; 5xFAD; eNOS; neprilysin; presenilin; TGF beta; VEGF; beta-secretase 1 |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 14 Aug 2025 09:08 |
| Last Modified: | 14 Aug 2025 09:08 |
| URI: | https://pred.uni-regensburg.de/id/eprint/65638 |
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