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Ferritin levels in the cerebrospinal fluid predict Alzheimer's disease outcomes and are regulated by APOE
Ayton S, Faux NG, Bush AI, Alzheimer's Disease Neuroimaging Initiative.. Nature communications, 2015-05-19
Topic: Amyloid, tau and blood-test diagnosis
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.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Ayton, S., Faux, N. G., Bush, A. I., & Alzheimer's Disease Neuroimaging Initiative. (2015). Ferritin levels in the cerebrospinal fluid predict Alzheimer's disease outcomes and are regulated by APOE. Nature communications. https://doi.org/10.1038/ncomms7760
Vancouver
Ayton S, Faux NG, Bush AI, Alzheimer's Disease Neuroimaging Initiative. Ferritin levels in the cerebrospinal fluid predict Alzheimer's disease outcomes and are regulated by APOE. Nature communications. 2015. doi:10.1038/ncomms7760. PMID: 25988319.
BibTeX
@article{ayton2015-25988319,
author = {Ayton, S. and Faux, N. G. and Bush, A. I. and {Alzheimer's Disease Neuroimaging Initiative}},
title = {{Ferritin levels in the cerebrospinal fluid predict Alzheimer's disease outcomes and are regulated by APOE}},
journal = {Nature communications},
year = {2015},
doi = {10.1038/ncomms7760},
pmid = {25988319},
url = {https://doi.org/10.1038/ncomms7760}
}
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Key findings
- 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.
Why it matters
In the ADNI cohort, higher baseline cerebrospinal fluid ferritin levels were linked to worse cognitive performance over 7 years and predicted conversion from mild cognitive impairment to Alzheimer's disease, and ferritin was elevated by the APOE-ɛ4 risk allele. This points to brain iron elevation as a possible mechanism, but it does not show that lowering iron treats or prevents the disease.
Study details
- Study designlongitudinal study
- Evidence strengthModerate
Limitations
This is an observational cohort study (the Alzheimer's Disease Neuroimaging Initiative), so it shows ferritin levels predict outcomes statistically, not that iron itself drives the disease.
How this study scored 68/100
Published in a leading specialty journal, and it is a longitudinal study following the same people over time. Scored zero for sample size, effect reported, studied in people and randomized / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Nature communications) |
| Journal's citation record | 4 / 4 | Nature Communications: journal h-index 747 (OpenAlex, 2026-10-29) |
| Study design | 7 / 12 | A longitudinal study following the same people over time |
| Strength of evidence | 3 / 5 | Rated “moderate” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 1 / 5 | 2015 — within 20 year(s) of the newest study here |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomized / blinded | 0 / 2 | No randomization or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 6 / 7 | Cited 328 times (OpenAlex, 2026-10-10) |
| Citations per year | 4 / 5 | 25.2 citations a year over 13 year(s) since 2015 |
| Impact for its field and year | 5 / 6 | Cited 20.6× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 3 / 6 | Cited by 11 other studies in this library |
| Still being cited | 3 / 4 | Cited 96 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Karen L. Bell: h-index 71 (OpenAlex, whole career) |
| Institution's track record | 3 / 3 | University of Washington: institution h-index 3,540 (OpenAlex) |
| Multicenter collaboration | 3 / 3 | OpenAlex lists 39 institution(s) in 5 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 25988319) |
| Free to read | 2 / 2 | Free to read |
| Total | 68 / 100 | — |
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