Oxidation of Iron under Physiologically Relevant Conditions in Biological Fluids from Healthy and Alzheimer's Disease Subjects

ACS Chem Neurosci. 2017 Apr 19;8(4):731-736. doi: 10.1021/acschemneuro.6b00411. Epub 2017 Jan 3.

Abstract

Ferroxidase activity has been reported to be altered in various biological fluids in neurodegenerative disease, but the sources contributing to the altered activity are uncertain. Here we assay fractions of serum and cerebrospinal fluid with a newly validated triplex ferroxidase assay. Our data indicate that while ceruloplasmin, a multicopper ferroxidase, is the predominant source of serum activity, activity in CSF predominantly derives from a <10 kDa component, specifically from polyanions such as citrate and phosphate. We confirm that in human biological samples, ceruloplasmin activity in serum is decreased in Alzheimer's disease, but in CSF a reduction of activity in Alzheimer's disease originates from the polyanion component.

Keywords: Ferroxidase; ceruloplasmin; iron; neurodegenerative disease; oxidation; polyanion.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / metabolism*
  • Cerebrospinal Fluid / enzymology*
  • Ceruloplasmin / analysis
  • Ceruloplasmin / metabolism*
  • Humans
  • Iron / metabolism*
  • Oxidation-Reduction
  • Serum / enzymology*

Substances

  • Iron
  • Ceruloplasmin