Plasma Hepcidin as a potential informative biomarker of Alzheimer disease and vascular dementia

Abstract Background Blood-based assays are expected to be integrated into clinical routines across various contexts, including Alzheimer’s disease (AD). Vascular dementia (VaD), which is the second most common cause leading to dementia after AD, could also significantly benefit from this advancement...

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Main Authors: Constance Delaby, Daniel Alcolea, Germain Busto, Audrey Gabelle, Xavier Ayrignac, Karim Bennys, Elena Muiño, Paula Villatoro, Israel Fernández-Cadenas, Nicolas Pradeilles, Shaima El Bounasri, Soraya Torres, Christophe Hirtz, Henrik Zetterberg, Alberto Lleó, Juan Fortea, Sylvain Lehmann
Format: Article
Language:English
Published: BMC 2025-02-01
Series:Alzheimer’s Research & Therapy
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Online Access:https://doi.org/10.1186/s13195-025-01696-9
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author Constance Delaby
Daniel Alcolea
Germain Busto
Audrey Gabelle
Xavier Ayrignac
Karim Bennys
Elena Muiño
Paula Villatoro
Israel Fernández-Cadenas
Nicolas Pradeilles
Shaima El Bounasri
Soraya Torres
Christophe Hirtz
Henrik Zetterberg
Alberto Lleó
Juan Fortea
Sylvain Lehmann
author_facet Constance Delaby
Daniel Alcolea
Germain Busto
Audrey Gabelle
Xavier Ayrignac
Karim Bennys
Elena Muiño
Paula Villatoro
Israel Fernández-Cadenas
Nicolas Pradeilles
Shaima El Bounasri
Soraya Torres
Christophe Hirtz
Henrik Zetterberg
Alberto Lleó
Juan Fortea
Sylvain Lehmann
author_sort Constance Delaby
collection DOAJ
description Abstract Background Blood-based assays are expected to be integrated into clinical routines across various contexts, including Alzheimer’s disease (AD). Vascular dementia (VaD), which is the second most common cause leading to dementia after AD, could also significantly benefit from this advancement. However, no informative fluid biomarker has been identified for VaD. Given the disruption of iron homeostasis in both AD and VaD, this study aims to characterize the potential of the iron-related hormone Hepcidin as a biomarker for these two conditions. We will compare its added value to established AT(N) blood biomarkers. Methods Blood biomarkers (amyloid-composite, p-Tau181, Neurofilament Light Chain [NfL] and Hepcidin) levels in blood were analyzed in two independent cohorts and compared between AD patients and non-AD individuals. Additionally, blood Hepcidin and NfL were evaluated in the contexts of VaD and CADASIL, with their relative diagnostic value assessed. Results Blood Hepcidin and NfL do not significantly increase the AUC obtained with both p-Tau181 and amyloid composite in the context of AD. In contrast, AUC for VaD diagnosis is significantly higher when combining these two blood biomarkers compared to NfL alone. Hepcidin was not significantly modified in CADASIL patients compared to control subjects. Conclusion Blood Hepcidin and NfL have limited interest in the clinical context of AD but determination of these biomarkers shows to be highly informative for the diagnosis of VaD. This result could have important implications for diagnosis and implementation of clinical trials.
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spelling doaj-art-e7dc8f0ae42d4278a098be8bccdba5042025-08-20T02:12:58ZengBMCAlzheimer’s Research & Therapy1758-91932025-02-0117111210.1186/s13195-025-01696-9Plasma Hepcidin as a potential informative biomarker of Alzheimer disease and vascular dementiaConstance Delaby0Daniel Alcolea1Germain Busto2Audrey Gabelle3Xavier Ayrignac4Karim Bennys5Elena Muiño6Paula Villatoro7Israel Fernández-Cadenas8Nicolas Pradeilles9Shaima El Bounasri10Soraya Torres11Christophe Hirtz12Henrik Zetterberg13Alberto Lleó14Juan Fortea15Sylvain Lehmann16Université de Montpellier, INM INSERM LBPC-PPC, IRMB CHU de MontpellierDepartment of Neurology, Sant Pau Memory Unit, Hospital de La Santa Creu I Sant Pau - IIB Sant PauDepartment of Neurology, Université de Montpellier, Inserm INM NeuroPEPs TeamDepartment of Neurology, Université de Montpellier, Inserm INM NeuroPEPs TeamDepartment of Neurology, Université de Montpellier, Inserm INM NeuroPEPs TeamDepartment of Neurology, Université de Montpellier, Inserm INM NeuroPEPs TeamInstitut d’Investigació Biomèdica Sant Pau (IIB SANT PAU), Farmacogenómica y Genética NeurovascularFarmacogenómica y Genética Neurovascular. Institut d’Investigació Biomèdica Sant Pau (IIB, SANT PAU)Farmacogenómica y Genética Neurovascular. Institut d’Investigació Biomèdica Sant Pau (IIB, SANT PAU)Université de Montpellier, INM INSERM LBPC-PPC, IRMB CHU de MontpellierDepartment of Neurology, Sant Pau Memory Unit, Hospital de La Santa Creu I Sant Pau - IIB Sant PauDepartment of Neurology, Sant Pau Memory Unit, Hospital de La Santa Creu I Sant Pau - IIB Sant PauUniversité de Montpellier, INM INSERM LBPC-PPC, IRMB CHU de MontpellierDepartment of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, the , Sahlgrenska Academy at the University of GothenburgDepartment of Neurology, Sant Pau Memory Unit, Hospital de La Santa Creu I Sant Pau - IIB Sant PauDepartment of Neurology, Sant Pau Memory Unit, Hospital de La Santa Creu I Sant Pau - IIB Sant PauUniversité de Montpellier, INM INSERM LBPC-PPC, IRMB CHU de MontpellierAbstract Background Blood-based assays are expected to be integrated into clinical routines across various contexts, including Alzheimer’s disease (AD). Vascular dementia (VaD), which is the second most common cause leading to dementia after AD, could also significantly benefit from this advancement. However, no informative fluid biomarker has been identified for VaD. Given the disruption of iron homeostasis in both AD and VaD, this study aims to characterize the potential of the iron-related hormone Hepcidin as a biomarker for these two conditions. We will compare its added value to established AT(N) blood biomarkers. Methods Blood biomarkers (amyloid-composite, p-Tau181, Neurofilament Light Chain [NfL] and Hepcidin) levels in blood were analyzed in two independent cohorts and compared between AD patients and non-AD individuals. Additionally, blood Hepcidin and NfL were evaluated in the contexts of VaD and CADASIL, with their relative diagnostic value assessed. Results Blood Hepcidin and NfL do not significantly increase the AUC obtained with both p-Tau181 and amyloid composite in the context of AD. In contrast, AUC for VaD diagnosis is significantly higher when combining these two blood biomarkers compared to NfL alone. Hepcidin was not significantly modified in CADASIL patients compared to control subjects. Conclusion Blood Hepcidin and NfL have limited interest in the clinical context of AD but determination of these biomarkers shows to be highly informative for the diagnosis of VaD. This result could have important implications for diagnosis and implementation of clinical trials.https://doi.org/10.1186/s13195-025-01696-9Alzheimer’s diseaseBlood biomarkersHepcidinNfLDiagnosisVascular dementia
spellingShingle Constance Delaby
Daniel Alcolea
Germain Busto
Audrey Gabelle
Xavier Ayrignac
Karim Bennys
Elena Muiño
Paula Villatoro
Israel Fernández-Cadenas
Nicolas Pradeilles
Shaima El Bounasri
Soraya Torres
Christophe Hirtz
Henrik Zetterberg
Alberto Lleó
Juan Fortea
Sylvain Lehmann
Plasma Hepcidin as a potential informative biomarker of Alzheimer disease and vascular dementia
Alzheimer’s Research & Therapy
Alzheimer’s disease
Blood biomarkers
Hepcidin
NfL
Diagnosis
Vascular dementia
title Plasma Hepcidin as a potential informative biomarker of Alzheimer disease and vascular dementia
title_full Plasma Hepcidin as a potential informative biomarker of Alzheimer disease and vascular dementia
title_fullStr Plasma Hepcidin as a potential informative biomarker of Alzheimer disease and vascular dementia
title_full_unstemmed Plasma Hepcidin as a potential informative biomarker of Alzheimer disease and vascular dementia
title_short Plasma Hepcidin as a potential informative biomarker of Alzheimer disease and vascular dementia
title_sort plasma hepcidin as a potential informative biomarker of alzheimer disease and vascular dementia
topic Alzheimer’s disease
Blood biomarkers
Hepcidin
NfL
Diagnosis
Vascular dementia
url https://doi.org/10.1186/s13195-025-01696-9
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