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

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Ayton, S; Faux, NG; Bush, AI; Alzheimer's Disease Neuroimaging Initiative,

Published Date

  • May 19, 2015

Published In

Volume / Issue

  • 6 /

Start / End Page

  • 6760 -

PubMed ID

  • 25988319

Pubmed Central ID

  • 25988319

Electronic International Standard Serial Number (EISSN)

  • 2041-1723

International Standard Serial Number (ISSN)

  • 2041-1723

Digital Object Identifier (DOI)

  • 10.1038/ncomms7760

Language

  • eng