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

Alzheimer's Disease Neuroimaging Initiative, Myron Weiner, Michael DeVous

Research output: Contribution to journalArticle

97 Citations (Scopus)

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 languageEnglish (US)
Article number6760
JournalNature Communications
Volume6
DOIs
StatePublished - May 19 2015

Fingerprint

cerebrospinal fluid
Cerebrospinal fluid
Ferritins
Cerebrospinal Fluid
Alzheimer Disease
Iron
iron
brain
Brain
impairment
Neuroimaging
pathogenesis
Apolipoproteins E
Longitudinal Studies
Disease Progression
progressions
Alleles
proteins

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Chemistry(all)
  • Physics and Astronomy(all)

Cite this

Ferritin levels in the cerebrospinal fluid predict Alzheimer's disease outcomes and are regulated by APOE. / Alzheimer's Disease Neuroimaging Initiative; Weiner, Myron; DeVous, Michael.

In: Nature Communications, Vol. 6, 6760, 19.05.2015.

Research output: Contribution to journalArticle

Alzheimer's Disease Neuroimaging Initiative ; Weiner, Myron ; DeVous, Michael. / Ferritin levels in the cerebrospinal fluid predict Alzheimer's disease outcomes and are regulated by APOE. In: Nature Communications. 2015 ; Vol. 6.
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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-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.",
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