eprintid: 10103842 rev_number: 15 eprint_status: archive userid: 608 dir: disk0/10/10/38/42 datestamp: 2020-07-07 09:23:33 lastmod: 2021-09-17 22:22:01 status_changed: 2020-07-07 09:23:33 type: article metadata_visibility: show creators_name: Chatterjee, P creators_name: Mohammadi, M creators_name: Goozee, K creators_name: Shah, TM creators_name: Sohrabi, HR creators_name: Dias, CB creators_name: Shen, K creators_name: Asih, PR creators_name: Dave, P creators_name: Pedrini, S creators_name: Ashton, NJ creators_name: Hye, A creators_name: Taddei, K creators_name: Lovejoy, DB creators_name: Zetterberg, H creators_name: Blennow, K creators_name: Martins, RN title: Serum Hepcidin Levels in Cognitively Normal Older Adults with High Neocortical Amyloid-β Load ispublished: pub divisions: UCL divisions: B02 divisions: C07 divisions: D07 divisions: F86 keywords: Alzheimer’s disease, amyloid deposits, hepcidin, iron dyshomeostasis, positron emission tomography note: This article is published online with Open Access and distributed under the terms of the Creative Commons Attribution Non-Commercial License (CC BY-NC 4.0) 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 APOEɛ4 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. date: 2020-06-06 date_type: published official_url: http://dx.doi.org/10.3233/JAD-200162 oa_status: green full_text_type: pub language: eng primo: open primo_central: open_green verified: verified_manual elements_id: 1793665 doi: 10.3233/JAD-200162 pii: JAD200162 lyricists_name: Zetterberg, Henrik lyricists_id: HZETT94 actors_name: Zetterberg, Henrik actors_name: Harriot, Anne-Marie actors_id: HZETT94 actors_id: AHARA72 actors_role: owner actors_role: impersonator full_text_status: public publication: Journal of Alzheimer's Disease volume: 76 number: 1 pagerange: 291-301 event_location: Netherlands citation: Chatterjee, P; Mohammadi, M; Goozee, K; Shah, TM; Sohrabi, HR; Dias, CB; Shen, K; ... Martins, RN; + view all <#> Chatterjee, P; Mohammadi, M; Goozee, K; Shah, TM; Sohrabi, HR; Dias, CB; Shen, K; Asih, PR; Dave, P; Pedrini, S; Ashton, NJ; Hye, A; Taddei, K; Lovejoy, DB; Zetterberg, H; Blennow, K; Martins, RN; - view fewer <#> (2020) Serum Hepcidin Levels in Cognitively Normal Older Adults with High Neocortical Amyloid-β Load. Journal of Alzheimer's Disease , 76 (1) pp. 291-301. 10.3233/JAD-200162 <https://doi.org/10.3233/JAD-200162>. Green open access document_url: https://discovery.ucl.ac.uk/id/eprint/10103842/1/jad_2020_76-1_jad-76-1-jad200162_jad-76-jad200162.pdf