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Is early-life iron exposure critical in neurodegeneration?

Abstract

The effects of iron deficiency are well documented, but relatively little is known about the long-term implications of iron overload during development. High levels of redox-active iron in the brain have been associated with neurodegenerative disorders, most notably Parkinson disease, yet a gradual increase in brain iron seems to be a feature of normal ageing. Increased brain iron levels might result from intake of infant formula that is excessively fortified with iron, thereby altering the trajectory of brain iron uptake and amplifying the risk of iron-associated neurodegeneration in later life. In this Perspectives article, we discuss the potential long-term implications of excessive iron intake in early life, propose the analysis of iron deposits in teeth as a method for retrospective determination of iron exposure during critical developmental windows, and call for evidence-based optimization of the chemical composition of infant dietary supplements.

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Figure 1: Mechanisms of uptake of dietary iron in the developing brain.
Figure 2: Proposed progression of iron accumulation in the brain when dietary iron levels vary at an early age.
Figure 3: A novel dental biomarker of metal intake in early life.

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Acknowledgements

The authors' research was supported by a University of Technology, Sydney Chancellor's Postdoctoral Fellowship to D.J.H.; a National Institute of Environmental Health Sciences grant (DP2ES025453—National Institute of Health Director's New Innovator Award; R00ES019597) to M.A.; a Michael J. Fox Foundation for Parkinson's Research grant to D.I.F.; Australian Research Council Linkage Project grants (LP100200254, LP120200081) to D.J.H. and P.A.D.; and Australian National Health and Medical Research Council grants to D.I.F. (APP1043992, APP1044542) and to A.I.B (APP1002222, GNT1037234, APP1044542).

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D.J.H. and M.A. researched the data for and wrote the article. N.I.J., D.I.F., P.A.D. and A.I.B. contributed to discussion of the content and the reviewing and/or editing of the manuscript before submission.

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Correspondence to Dominic J. Hare.

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D.I.F. is a paid consultant to and a shareholder of Prana Biotechnology. A.I.B. is a shareholder of Prana Biotechnology, Mesoblast, Cogstate, Brighton and Eucalyptus, and is a paid consultant for Collaborative Medicinal Discovery and Brighton. D.J.H., M.A., N.L.J. and P.A.D. declare no competing interests.

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Hare, D., Arora, M., Jenkins, N. et al. Is early-life iron exposure critical in neurodegeneration?. Nat Rev Neurol 11, 536–544 (2015). https://doi.org/10.1038/nrneurol.2015.100

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