Alteration of Iron Concentration in Alzheimer's Disease as a Possible Diagnostic Biomarker Unveiling Ferroptosis

Int J Mol Sci. 2021 Apr 25;22(9):4479. doi: 10.3390/ijms22094479.

Abstract

Proper functioning of all organs, including the brain, requires iron. It is present in different forms in biological fluids, and alterations in its distribution can induce oxidative stress and neurodegeneration. However, the clinical parameters normally used for monitoring iron concentration in biological fluids (i.e., serum and cerebrospinal fluid) can hardly detect the quantity of circulating iron, while indirect measurements, e.g., magnetic resonance imaging, require further validation. This review summarizes the mechanisms involved in brain iron metabolism, homeostasis, and iron imbalance caused by alterations detectable by standard and non-standard indicators of iron status. These indicators for iron transport, storage, and metabolism can help to understand which biomarkers can better detect iron imbalances responsible for neurodegenerative diseases.

Keywords: Alzheimer’s disease; biomarkers; ferroptosis; iron; neurodegeneration.

Publication types

  • Review

MeSH terms

  • Alzheimer Disease / diagnosis*
  • Alzheimer Disease / metabolism
  • Biomarkers / blood*
  • Biomarkers / cerebrospinal fluid
  • Brain / metabolism*
  • Brain / pathology
  • Ceruloplasmin / deficiency
  • Ceruloplasmin / metabolism
  • Ferritins / blood
  • Ferritins / cerebrospinal fluid
  • Ferritins / metabolism
  • Ferroptosis / physiology*
  • Humans
  • Iron / blood
  • Iron / cerebrospinal fluid
  • Iron / metabolism*
  • Iron Metabolism Disorders / metabolism
  • Magnetic Resonance Imaging
  • Neurodegenerative Diseases / metabolism
  • Oxidative Stress / physiology
  • Transferrin / cerebrospinal fluid
  • Transferrin / metabolism

Substances

  • Biomarkers
  • Transferrin
  • Ferritins
  • Iron
  • Ceruloplasmin

Supplementary concepts

  • Familial apoceruloplasmin deficiency