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Elevated plasma ferritin in elderly individuals with high neocortical amyloid-β load

Molecular Psychiatry volume 23, pages 1807–1812 (2018)Cite this article

Abstract

Ferritin, an iron storage and regulation protein, has been associated with Alzheimer’s disease (AD); however, it has not been investigated in preclinical AD, detected by neocortical amyloid-β load (NAL), before cognitive impairment. Cross-sectional analyses were carried out for plasma and serum ferritin in participants in the Kerr Anglican Retirement Village Initiative in Aging Health cohort. Subjects were aged 65–90 years and were categorized into high and low NAL groups via positron emission tomography using a standard uptake value ratio cutoff=1.35. Ferritin was significantly elevated in participants with high NAL compared with those with low NAL, adjusted for covariates age, sex, apolipoprotein E ɛ4 carriage and levels of C-reactive protein (an inflammation marker). Ferritin was also observed to correlate positively with NAL. 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 plasma ferritin was added to the base model (AUC=0.810), such that at 75% sensitivity, the specificity increased from 62 to 71% on adding ferritin to the base model, indicating that ferritin is a statistically significant additional predictor of NAL over and above the base model. However, ferritin’s contribution alone is relatively minor compared with the base model. The current findings suggest that impaired iron mobilization is an early event in AD pathogenesis. Observations from the present study highlight ferritin’s potential to contribute to a blood biomarker panel for preclinical AD.

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Acknowledgments

This study was funded by the Anglicare, Sydney, the McCusker Alzheimer Research Foundation (MARF), Perth and the KaRa Institute of Neurological Diseases (KaRa MINDS), Sydney. We sincerely thank Professor David Lovejoy for reviewing the manuscript. We thank the participants and their families for their participation and cooperation, and the Anglicare, KaRa MINDS and MARF research and support staff for their contributions to this study. We specially thank Bethany Ball, Emma Toovey, Kate Fredericks and Catherine Brown for their contributions to this study. We also thank the staff of the Macquarie Medical Imaging centre in Macquarie University Hospital, Sydney, for their contributions. KG is a recipient of the Cooperative Research Centre for Mental Health top-up scholarship. AIB is funded by the Australian National Health and Medical Research Council. Florbetaben is a proprietary PET radiopharmaceutical owned by Piramal Imaging SA. For this study, Florbetaben was manufactured and supplied under GMP conditions by Cyclotek (Aust) Pty Ltd.

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  1. These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Biomedical Sciences, Macquarie University, Sydney, NSW, Australia

    K Goozee, P Chatterjee, H R Sohrabi, P Dave, R Chung & R N Martins

  2. Anglicare, Sydney, NSW, Australia

    K Goozee, P Dave & C ManYan

  3. School of Psychiatry and Clinical Neurosciences, University of Western Australia, Perth, WA, Australia

    K Goozee & R N Martins

  4. School of Medical Health and Sciences, Edith Cowan University, Perth, WA, Australia

    K Goozee, P Chatterjee, H R Sohrabi, K Taddei & R N Martins

  5. McCusker Alzheimer Research Foundation, Perth, WA, Australia

    K Goozee, H R Sohrabi, K Taddei & R N Martins

  6. KaRa Institute of Neurological Disease, Sydney, NSW, Australia

    K Goozee, P Chatterjee, P R Asih & R N Martins

  7. The Cooperative Research Centre for Mental Health, Carlton, VIC, Australia

    K Goozee, H R Sohrabi, A I Bush & R N Martins

  8. Institute for Immunology and Infectious Diseases, Murdoch University, Perth, WA, Australia

    I James

  9. Australian eHealth Research Centre, CSIRO, Floreat, WA, Australia

    K Shen

  10. School of Medical Sciences, University of New South Wales, Sydney, NSW, Australia

    P R Asih & J B Kwok

  11. Florey Department of Neuroscience and Mental Health, University of Melbourne University, Melbourne, VIC, Australia

    S J Ayton & A I Bush

  12. Nutraceuticals Research Program, School of Biomedical Sciences and Pharmacy, University of Newcastle, Callaghan, NSW, Australia

    M L Garg

  13. Neuroscience Research Australia, Sydney, NSW, Australia

    J B Kwok

  14. Department of Clinical Medicine, Macquarie University, Sydney, NSW, Australia

    J S Magnussen

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  1. K Goozee
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Correspondence to R N Martins.

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Goozee, K., Chatterjee, P., James, I. et al. Elevated plasma ferritin in elderly individuals with high neocortical amyloid-β load. Mol Psychiatry 23, 1807–1812 (2018). https://doi.org/10.1038/mp.2017.146

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