Publication Type Academic Article
Authors Ayton S, Faux N, Bush A
Journal Nat Commun
Volume 6
Pagination 6760
Date Published 05/19/2015
ISSN 2041-1723
Keywords Alzheimer Disease, Apolipoproteins E, Ferritins, Gene Expression Regulation
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.
DOI 10.1038/ncomms7760
PubMed ID 25988319
PubMed Central ID PMC4479012
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