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Background <p>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.</p> Methods <p>Blood biomarkers (amyloid-composite, p-Tau<sub>181</sub>, 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.</p> Results <p>Blood Hepcidin and NfL do not significantly increase the AUC obtained with both p-Tau<sub>181</sub> 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.</p> Conclusion <p>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.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年2月13日

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  • 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

摘要

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.