Associations Between Hepatic Functions and Plasma Amyloid-Beta Levels-Implications for the Capacity of Liver in Peripheral Amyloid-Beta Clearance

Mol Neurobiol. 2017 Apr;54(3):2338-2344. doi: 10.1007/s12035-016-9826-1. Epub 2016 Mar 9.

Abstract

Amyloid-beta (Aβ) plays a pivotal role in the pathogenesis of Alzheimer's disease (AD). Clearance of Aβ is a promising therapeutic strategy for AD. We have previously demonstrated that peripheral organs play important roles in the clearance of brain-derived Aβ. In the present study, we recruited 46 patients with liver cirrhosis and 46 normal controls and found that plasma Aβ40 and Aβ42 levels were significantly higher in the cirrhosis patients than in the normal controls. Notably, cirrhosis patients with hepatitis B virus (HBV) infection had higher plasma Aβ40 and Aβ42 levels than HBV-negative cirrhosis patients. Besides, cirrhosis patients had significantly higher plasma levels of interleukin-1β (IL-1β) and IL-6. Plasma tumor necrosis factor α (TNF-α) and interferon-γ (IFN-γ) levels were not significantly different between the groups. Moreover, we found significant correlations of hepatic functions with plasma Aβ40 and Aβ42 levels. Plasma IL-6 levels were also significantly correlated with plasma Aβ40 levels. However, in the linear regression model, we found significant correlation of plasma Aβ40 levels with hepatic functions, but not with plasma IL-6 levels. Our results indicate that the hepatic dysfunctions might result in decreased peripheral Aβ clearance by the liver. Protecting hepatic functions might be helpful for the clearance of brain-derived Aβ in the blood.

Keywords: Alzheimer’s disease; Amyloid-beta; Hepatic dysfunction; Liver cirrhosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Alzheimer Disease / metabolism*
  • Alzheimer Disease / pathology
  • Amyloid beta-Peptides / blood*
  • Brain / metabolism*
  • Female
  • Humans
  • Interferon-gamma / blood
  • Interleukin-1beta / blood
  • Interleukin-6 / metabolism
  • Liver / metabolism*
  • Male
  • Middle Aged
  • Peptide Fragments / metabolism
  • Tumor Necrosis Factor-alpha / blood

Substances

  • Amyloid beta-Peptides
  • IL6 protein, human
  • Interleukin-1beta
  • Interleukin-6
  • Peptide Fragments
  • Tumor Necrosis Factor-alpha
  • Interferon-gamma