Antifibrotic Effects of Amyloid-Beta and Its Loss in Cirrhotic Liver

Gayane Hrachia Buniatian, Ralf Weiskirchen, Thomas S. Weiss, Ute Schwinghammer, Martin Fritz, Torgom Seferyan, Barbara Proksch, Michael Glaser, Ali Lourhmati, Marine Buadze, Erawan Borkham-Kamphorst, Frank Gaunitz, Christoph H. Gleiter, Thomas Lang, Elke Schaeffeler, Roman Tremmel, Holger Cynis, William H. Frey, Rolf Gebhardt, Scott L. FriedmanWolfgang Mikulits, Matthias Schwab, Lusine Danielyan

Research output: Contribution to journalArticlepeer-review

4 Scopus citations


The function and regulation of amyloid-beta (Aβ) in healthy and diseased liver remains unexplored. Because Aβ reduces the integrity of the blood-brain barrier we have examined its potential role in regulating the sinusoidal permeability of normal and cirrhotic liver. Aβ and key proteins that generate (beta-secretase 1 and presenilin-1) and degrade it (neprilysin and myelin basic protein) were decreased in human cirrhotic liver. In culture, activated hepatic stellate cells (HSC) internalized Aβ more efficiently than astrocytes and HSC degraded Aβ leading to suppressed expression of α-smooth muscle actin (α-SMA), collagen 1 and transforming growth factor β (TGFβ). Aβ also upregulated sinusoidal permeability marker endothelial NO synthase (eNOS) and decreased TGFβ in cultured human liver sinusoidal endothelial cells (hLSEC). Liver Aβ levels also correlate with the expression of eNOS in transgenic Alzheimer's disease mice and in human and rodent cirrhosis/fibrosis. These findings suggest a previously unexplored role of Aβ in the maintenance of liver sinusoidal permeability and in protection against cirrhosis/fibrosis via attenuation of HSC activation.

Original languageEnglish
Article number2638
Issue number2
StatePublished - 17 Feb 2020


  • Alzheimer’s disease
  • astrocytes
  • beta secretase
  • endothelial nitric oxide synthase
  • hepatic stellate cells
  • liver cirrhosis
  • liver sinusoidal endothelial cells
  • liver sinusoidal permeability
  • myelin basic protein
  • neprilysin
  • presenilin


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