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Ferritin levels in the cerebrospinal fluid predict Alzheimer’s disease outcomes and are regulated by APOE

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  • Scott Ayton

    (Oxidation Biology Unit, The Florey Institute for Neuroscience and Mental Health, The University of Melbourne)

  • Noel G. Faux

    (Bioinformatics Core, The Florey Institute for Neuroscience and Mental Health, The University of Melbourne
    Cooperative Research Center for Mental Health, Parkville, Victoria 3052)

  • Ashley I. Bush

    (Oxidation Biology Unit, The Florey Institute for Neuroscience and Mental Health, The University of Melbourne
    Cooperative Research Center for Mental Health, Parkville, Victoria 3052)

Abstract

Brain iron elevation is implicated in Alzheimer’s disease (AD) pathogenesis, but the impact of iron on disease outcomes has not been previously explored in a longitudinal study. Ferritin is the major iron storage protein of the body; by using cerebrospinal fluid (CSF) levels of ferritin as an index, we explored whether brain iron status impacts longitudinal outcomes in the Alzheimer’s Disease Neuroimaging Initiative (ADNI) cohort. We show that baseline CSF ferritin levels were negatively associated with cognitive performance over 7 years in 91 cognitively normal, 144 mild cognitive impairment (MCI) and 67 AD subjects, and predicted MCI conversion to AD. Ferritin was strongly associated with CSF apolipoprotein E levels and was elevated by the Alzheimer’s risk allele, APOE-ɛ4. These findings reveal that elevated brain iron adversely impacts on AD progression, and introduce brain iron elevation as a possible mechanism for APOE-ɛ4 being the major genetic risk factor for AD.

Suggested Citation

  • Scott Ayton & Noel G. Faux & Ashley I. Bush, 2015. "Ferritin levels in the cerebrospinal fluid predict Alzheimer’s disease outcomes and are regulated by APOE," Nature Communications, Nature, vol. 6(1), pages 1-9, November.
    • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms7760
    DOI: 10.1038/ncomms7760
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