Serum hepcidin levels, iron dyshomeostasis and cognitive loss in Alzheimer'S Disease

Zohara Sternberg, Zihua Hu, Daniel Sternberg, Shayan Waseh, Joseph Quinn, Katherine Wild, Jeffrey Kaye, Lin Zhao, Michael Garrick

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

This pilot study examined the status of the master iron regulatory peptide, hepcidin, and peripheral related iron parameters in Alzheimer's disease (AD) and mild cognitive impairment patients, and evaluated the relationship between iron dyshomeostasis and amyloid-beta (Aβ), cognitive assessment tests, neuroimaging and clinical data. Frozen serum samples from the Oregon Tissue Bank were used to measure serum levels of hepcidin, ferritin, Aβ40, Aβ42 using enzyme-linked immunosorbent assay. Serum transferrin levels were determined indirectly as total iron binding capacity, serum iron was measured and the percent saturation of transferrin calculated. The study variables were correlated with the patients' existing cognitive assessment tests, neuroimaging, and clinical data. Hepcidin, and iron-related proteins tended to be higher in AD patients than controls, reaching statistical significance for ferritin, whereas Aβ40, Aβ42 serum levels tended to be lower. Patients with pure AD had three times higher serum hepcidin levels than controls; gender differences in hepcidin and iron-related proteins were observed. Patient stratification based on clinical dementia rating-sum of boxes revealed significantly higher levels of iron and iron-related proteins in AD patients in the upper 50% as compared to controls, suggesting that iron dyshomeostasis worsens as cognitive impairment increases. Unlike Aβ peptides, iron and iron-related proteins showed significant association with cognitive assessment tests, neuroimaging, and clinical data. Hepcidin and iron-related proteins comprise a group of serum biomarkers that relate to AD diagnosis and AD disease progression. Future studies should determine whether strategies targeted to diminishing hepcidin synthesis/secretion and improving iron homeostasis could have a beneficial impact on AD progression.

Original languageEnglish (US)
Pages (from-to)215-227
Number of pages13
JournalAging and Disease
Volume8
Issue number2
DOIs
StatePublished - 2017

Fingerprint

Hepcidins
Alzheimer Disease
Iron
Serum
Neuroimaging
Transferrin
Ferritins
Proteins
Disease Progression
Tissue Banks
Peptides
Amyloid

Keywords

  • Alzheimer's disease
  • Ferritin
  • Inflammation
  • Iron homeostasis
  • Mild cognitive impairment
  • Percent transferrin saturation
  • Serum biomarker

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Geriatrics and Gerontology
  • Clinical Neurology
  • Cell Biology

Cite this

Serum hepcidin levels, iron dyshomeostasis and cognitive loss in Alzheimer'S Disease. / Sternberg, Zohara; Hu, Zihua; Sternberg, Daniel; Waseh, Shayan; Quinn, Joseph; Wild, Katherine; Kaye, Jeffrey; Zhao, Lin; Garrick, Michael.

In: Aging and Disease, Vol. 8, No. 2, 2017, p. 215-227.

Research output: Contribution to journalArticle

Sternberg, Zohara ; Hu, Zihua ; Sternberg, Daniel ; Waseh, Shayan ; Quinn, Joseph ; Wild, Katherine ; Kaye, Jeffrey ; Zhao, Lin ; Garrick, Michael. / Serum hepcidin levels, iron dyshomeostasis and cognitive loss in Alzheimer'S Disease. In: Aging and Disease. 2017 ; Vol. 8, No. 2. pp. 215-227.
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