Excessive early-life dietary exposure: a potential source of elevated brain iron and a risk factor for Parkinson's disease

Dominic J Hare; Bárbara Rita Cardoso; Erika P Raven; Kay L Double; David I Finkelstein; Ewa A Szymlek-Gay; Beverley-Ann Biggs

doi:10.1038/s41531-016-0004-y

Excessive early-life dietary exposure: a potential source of elevated brain iron and a risk factor for Parkinson's disease

NPJ Parkinsons Dis. 2017 Jan 5:3:1. doi: 10.1038/s41531-016-0004-y. eCollection 2017.

Authors

Dominic J Hare^{1

2

3}, Bárbara Rita Cardoso^{2

4}, Erika P Raven^{5

6}, Kay L Double^{7

8}, David I Finkelstein², Ewa A Szymlek-Gay⁹, Beverley-Ann Biggs^{1

10}

Affiliations

¹ Department of Medicine (Royal Melbourne Hospital) at the Doherty Institute, The University of Melbourne, Parkville, Melbourne, VIC Australia.
² The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, Melbourne, VIC Australia.
³ Elemental Bio-imaging Facility, University of Technology Sydney, Broadway, NSW Australia.
⁴ Department of Pharmaceutical Sciences, Department of Food and Experimental Nutrition, University of São Paulo, São Paulo, Brazil.
⁵ Center for Functional and Molecular Imaging, Georgetown University Medical Centre, Washington DC, USA.
⁶ Advanced Magnetic Resonance Imaging Section, Laboratory of Functional and Molecular Imaging, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD USA.
⁷ Sydney Medical School, University of Sydney, Darlington, NSW Australia.
⁸ Brain and Mind Centre, University of Sydney, Camperdown, NSW Australia.
⁹ Institute for Physical Activity and Nutrition, School of Exercise and Nutrition Sciences, Deakin University, Geelong, VIC Australia.
¹⁰ Victorian Infectious Diseases Service, Royal Melbourne Hospital, Parkville, Melbourne, VIC Australia.

Abstract

Iron accumulates gradually in the ageing brain. In Parkinson's disease, iron deposition within the substantia nigra is further increased, contributing to a heightened pro-oxidant environment in dopaminergic neurons. We hypothesise that individuals in high-income countries, where cereals and infant formulae have historically been fortified with iron, experience increased early-life iron exposure that predisposes them to age-related iron accumulation in the brain. Combined with genetic factors that limit iron regulatory capacity and/or dopamine metabolism, this may increase the risk of Parkinson's diseases. We propose to (a) validate a retrospective biomarker of iron exposure in children; (b) translate this biomarker to adults; (c) integrate it with in vivo brain iron in Parkinson's disease; and (d) longitudinally examine the relationships between early-life iron exposure and metabolism, brain iron deposition and Parkinson's disease risk. This approach will provide empirical evidence to support therapeutically addressing brain iron deposition in Parkinson's diseases and produce a potential biomarker of Parkinson's disease risk in preclinical individuals.