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Ferritin levels in the cerebrospinal fluid predict Alzheimer's disease outcomes and are regulated by APOE.
Nat Commun 2015; 6:6760NC

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.

Authors+Show Affiliations

Oxidation Biology Unit, The Florey Institute for Neuroscience and Mental Health, The University of Melbourne, Parkville, Victoria 3052, Australia.1] Bioinformatics Core, The Florey Institute for Neuroscience and Mental Health, The University of Melbourne, Parkville, Victoria 3052, Australia [2] Cooperative Research Center for Mental Health, Parkville, Victoria 3052, Australia.1] Oxidation Biology Unit, The Florey Institute for Neuroscience and Mental Health, The University of Melbourne, Parkville, Victoria 3052, Australia [2] Cooperative Research Center for Mental Health, Parkville, Victoria 3052, Australia.No affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

Language

eng

PubMed ID

25988319

Citation

Ayton, Scott, et al. "Ferritin Levels in the Cerebrospinal Fluid Predict Alzheimer's Disease Outcomes and Are Regulated By APOE." Nature Communications, vol. 6, 2015, p. 6760.
Ayton S, Faux NG, Bush AI, et al. Ferritin levels in the cerebrospinal fluid predict Alzheimer's disease outcomes and are regulated by APOE. Nat Commun. 2015;6:6760.
Ayton, S., Faux, N. G., & Bush, A. I. (2015). Ferritin levels in the cerebrospinal fluid predict Alzheimer's disease outcomes and are regulated by APOE. Nature Communications, 6, p. 6760. doi:10.1038/ncomms7760.
Ayton S, et al. Ferritin Levels in the Cerebrospinal Fluid Predict Alzheimer's Disease Outcomes and Are Regulated By APOE. Nat Commun. 2015 May 19;6:6760. PubMed PMID: 25988319.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Ferritin levels in the cerebrospinal fluid predict Alzheimer's disease outcomes and are regulated by APOE. AU - Ayton,Scott, AU - Faux,Noel G, AU - Bush,Ashley I, AU - ,, Y1 - 2015/05/19/ PY - 2014/10/31/received PY - 2015/02/25/accepted PY - 2015/5/20/entrez PY - 2015/5/20/pubmed PY - 2016/3/26/medline SP - 6760 EP - 6760 JF - Nature communications JO - Nat Commun VL - 6 N2 - 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. SN - 2041-1723 UR - https://www.unboundmedicine.com/medline/citation/25988319/full_citation L2 - http://dx.doi.org/10.1038/ncomms7760 DB - PRIME DP - Unbound Medicine ER -