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Lipid membranes accelerate amyloid formation in the mouse model of AA amyloidosis

Aida Vahdat Shariat Panahi1,2, Per Hultman3, Karin Öllinger1

  • 1a Experimental Pathology, Department of Clinical and Experimental Medicine , Linköping University , Linköping , Sweden.

Amyloid : the International Journal of Experimental and Clinical Investigation : the Official Journal of the International Society of Amyloidosis
|April 2, 2019
PubMed
Abstract

Insights

Lipid membranes accelerate AA amyloidosis formation in mice. This study highlights increased intracellular lipid content as a facilitator of AA amyloid fibril formation.

Area of Science:

  • Biochemistry
  • Immunology
  • Cell Biology

Background:

  • AA amyloidosis results from chronic inflammation, characterized by serum amyloid A (SAA) protein fragment deposition.
  • Macrophages are observed near amyloid deposits, suggesting a role in amyloid formation or degradation.
  • Lipid membranes are increasingly recognized for their ability to accelerate amyloid protein fibrillation.

Purpose of the Study:

  • To investigate the role of liposomes and amyloid-enhancing factor (AEF) in accelerating AA amyloidosis.
  • To compare the amyloidogenic effects of liposomes versus AEF in an experimental mouse model.

Main Methods:

  • An experimental mouse model of AA amyloidosis was utilized.
  • Inflammation was induced using silver nitrate, followed by intravenous administration of liposomes and/or AEF.
  • Amyloid formation and deposition patterns were analyzed in spleen tissues.

Main Results:

  • Liposomes were found to accelerate amyloid formation in inflamed mice, though less effectively than AEF.
  • Amyloid deposits predominantly occurred in splenic marginal zones, correlating with marginal zone macrophage depletion.
  • Red pulp macrophages and metallophilic marginal zone macrophages remained unaffected by amyloid deposition.

Conclusions:

  • Elevated intracellular lipid content promotes the formation of AA amyloid fibrils.
  • The employed mouse model of AA amyloidosis is suitable for detailed mechanistic investigations into amyloidogenesis.
Keywords:
AA amyloidosisAmyloidlipid membraneliposomesmacrophages

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