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-ε4. These findings reveal that elevated brain iron adversely impacts on AD progression, and introduce brain iron elevation as a possible mechanism for APOE-ε4 being the major genetic risk factor for AD.
| Original language | English (US) |
|---|---|
| Article number | 6760 |
| Journal | Nature Communications |
| Volume | 6 |
| DOIs | |
| State | Published - May 19 2015 |
ASJC Scopus subject areas
- General Chemistry
- General Biochemistry, Genetics and Molecular Biology
- General Physics and Astronomy
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In: Nature Communications, Vol. 6, 6760, 19.05.2015.
Research output: Contribution to journal › Article › peer-review
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TY - JOUR
T1 - Ferritin levels in the cerebrospinal fluid predict Alzheimer's disease outcomes and are regulated by APOE
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N1 - Publisher Copyright: © 2015 Macmillan Publishers Limited. All rights reserved.
PY - 2015/5/19
Y1 - 2015/5/19
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-ε4. These findings reveal that elevated brain iron adversely impacts on AD progression, and introduce brain iron elevation as a possible mechanism for APOE-ε4 being the major genetic risk factor for AD.
AB - 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-ε4. These findings reveal that elevated brain iron adversely impacts on AD progression, and introduce brain iron elevation as a possible mechanism for APOE-ε4 being the major genetic risk factor for AD.
UR - http://www.scopus.com/inward/record.url?scp=84930225631&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84930225631&partnerID=8YFLogxK
U2 - 10.1038/ncomms7760
DO - 10.1038/ncomms7760
M3 - Article
C2 - 25988319
AN - SCOPUS:84930225631
SN - 2041-1723
VL - 6
JO - Nature Communications
JF - Nature Communications
M1 - 6760
ER -