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