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

Scott Ayton; Noel G Faux; Ashley I Bush; Alzheimer's Disease Neuroimaging Initiative

doi:10.1038/ncomms7760

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

Journal article

Open access

Peer reviewed

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

Scott Ayton, Noel G Faux, Ashley I Bush and Alzheimer's Disease Neuroimaging Initiative

Nature communications, Vol.6(1), pp.6760-6760

05/19/2015

DOI: 10.1038/ncomms7760

PMCID: PMC4479012

PMID: 25988319

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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.

Magnetic Resonance Imaging

Cognition Disorders - cerebrospinal fluid

Ferritins - cerebrospinal fluid

Humans

Middle Aged

Risk Factors

Gene Expression Regulation

Genotype

Male

Treatment Outcome

Cognition

Alzheimer Disease - cerebrospinal fluid

Atrophy

Brain - metabolism

Iron - cerebrospinal fluid

Apolipoproteins E - genetics

Aged, 80 and over

Female

Aged

Longitudinal Studies

Cohort Studies

Databases, Factual

Details

Title: Subtitle: Ferritin levels in the cerebrospinal fluid predict Alzheimer's disease outcomes and are regulated by APOE
Creators: Scott Ayton - Oxidation Biology Unit, The Florey Institute for Neuroscience and Mental Health, The University of Melbourne, Parkville, Victoria 3052, Australia
Noel G Faux - 1] Bioinformatics Core, The Florey Institute for Neuroscience and Mental Health, The University of Melbourne, Parkville, Victoria 3052, Australia Cooperative Research Center for Mental Health, Parkville, Victoria 3052, Australia
Ashley I Bush - 1] Oxidation Biology Unit, The Florey Institute for Neuroscience and Mental Health, The University of Melbourne, Parkville, Victoria 3052, Australia Cooperative Research Center for Mental Health, Parkville, Victoria 3052, Australia
Alzheimer's Disease Neuroimaging Initiative
Contributors: Laura L Boles-Ponto (Contributor) - University of Iowa, Radiology
HyungSub Shim (Contributor) - University of Iowa, Neurology
Resource Type: Journal article
Publication Details: Nature communications, Vol.6(1), pp.6760-6760
DOI: 10.1038/ncomms7760
PMID: 25988319
PMCID: PMC4479012
NLM abbreviation: Nat Commun
ISSN: 2041-1723
eISSN: 2041-1723
Publisher: England
Grant note: P30 AG062421 / NIA NIH HHS P50 AG005134 / NIA NIH HHS UL1 TR001422 / NCATS NIH HHS P30 AG013846 / NIA NIH HHS U01 AG024904 / NIA NIH HHS
Language: English
Date published: 05/19/2015
Academic Unit: Neurology; Radiology; Psychiatry; Pharmaceutical Sciences and Experimental Therapeutics
Record Identifier: 9984013206402771

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