title: Serum Hepcidin Levels, Iron Dyshomeostasis and Cognitive Loss in Alzheimer's Disease.
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.
authors.affiliation: 1Department of Neurology, Stroke Center, Buffalo Medical Center, Buffalo, NY, USA.
authors.forename: Zohara
authors.initials: Z
authors.lastname: Sternberg
authors.affiliation: 2Center for Computational Research, New York State Center for Excellence in Bioinformatics and Life Sciences, University at Buffalo, Buffalo, NY, USA.
authors.forename: Zihua
authors.initials: Z
authors.lastname: Hu
authors.affiliation: 1Department of Neurology, Stroke Center, Buffalo Medical Center, Buffalo, NY, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Sternberg
authors.affiliation: 3Department of Biology, State University of New York at Buffalo, Buffalo, NY 14260 USA.
authors.forename: Shayan
authors.initials: S
authors.lastname: Waseh
authors.affiliation: 4Layton Aging & Alzheimer's Research Center, Oregon Health and Science University, Portland, Oregon, USA.
authors.forename: Joseph F
authors.initials: JF
authors.lastname: Quinn
authors.affiliation: 4Layton Aging & Alzheimer's Research Center, Oregon Health and Science University, Portland, Oregon, USA.
authors.forename: Katharine
authors.initials: K
authors.lastname: Wild
authors.affiliation: 4Layton Aging & Alzheimer's Research Center, Oregon Health and Science University, Portland, Oregon, USA.
authors.forename: Kaye
authors.initials: K
authors.lastname: Jeffrey
authors.affiliation: 5Department of Biochemistry, State University of New York at Buffalo, Buffalo, NY 14214 USA.
authors.forename: Lin
authors.initials: L
authors.lastname: Zhao
authors.affiliation: 5Department of Biochemistry, State University of New York at Buffalo, Buffalo, NY 14214 USA.; 6Department of Pediatrics, State University of New York at Buffalo, Buffalo, NY 14214 USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Garrick
keywords: Alzheimer’s disease; Ferritin; Inflammation; Iron homeostasis; Mild cognitive impairment; Percent transferrin saturation; Serum biomarker