Serum Hepcidin Levels in Cognitively Normal Older Adults with High Neocortical Amyloid-β Load

Pratishtha Chatterjee, Maryam Mohammadi, Kathryn Goozee, Tejal M. Shah, Hamid R. Sohrabi, Cintia B. Dias, Kaikai Shen, Prita R. Asih, Preeti Dave, Steve Pedrini, Nicholas J. Ashton, Abdul Hye, Kevin Taddei, David B. Lovejoy, Henrik Zetterberg, Kaj Blennow, Ralph N. Martins

Research output: Contribution to journalArticlepeer-review

5 Citations (Scopus)

Abstract

Background/Objective: Hepcidin, an iron-regulating hormone, suppresses the release of iron by binding to the iron exporter protein, ferroportin, resulting in intracellular iron accumulation. Given that iron dyshomeostasis has been observed in Alzheimer's disease (AD) together with elevated serum hepcidin levels, the current study examined whether elevated serum hepcidin levels are an early event in AD pathogenesis by measuring the hormone in cognitively normal older adults at risk of AD, based on high neocortical amyloid-β load (NAL). Methods: Serum hepcidin levels in cognitively normal participants (n = 100) aged between 65-90 years were measured using ELISA. To evaluate NAL, all participants underwent 18F-florbetaben positron emission tomography. A standard uptake value ratio (SUVR)<1.35 was classified as low NAL (n = 65) and ≥1.35 (n = 35) was classified as high NAL. Results: Serum hepcidin was significantly higher in participants with high NAL compared to those with low NAL before and after adjusting for covariates: age, gender, and APOE ϵ4 carriage (p < 0.05). A receiver operating characteristic curve based on a logistic regression of the same covariates, the base model, distinguished high from low NAL (area under the curve, AUC = 0.766), but was outperformed when serum hepcidin was added to the base model (AUC = 0.794) and further improved with plasma Aβ42/40 ratio (AUC = 0.829). Conclusion: The present findings indicate that serum hepcidin is increased in individuals at risk for AD and contribute to the body of evidence supporting iron dyshomeostasis as an early event of AD. Further, hepcidin may add value to a panel of markers that contribute toward identifying individuals at risk of AD; however, further validation studies are required.

Original languageEnglish
Pages (from-to)291-301
Number of pages11
JournalJournal of Alzheimer's Disease
Volume76
Issue number1
DOIs
Publication statusPublished - 2020

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