Colocalization of cerebral iron with Amyloid beta in Mild Cognitive Impairment

Sci Rep. 2016 Oct 17:6:35514. doi: 10.1038/srep35514.

Abstract

Quantitative Susceptibility Mapping (QSM) MRI at 7 Tesla and 11-Carbon Pittsburgh-Compound-B PET were used for investigating the relationship between brain iron and Amyloid beta (Aβ) plaque-load in a context of increased risk for Alzheimer's disease (AD), as reflected by the Apolipoprotein E ε4 (APOE-e4) allele and mild cognitive impairment (MCI) in elderly subjects. Carriers of APOE-e4 with normal cognition had higher cortical Aβ-plaque-load than non-carriers. In MCI an association between APOE-e4 and higher Aβ-plaque-load was observable both for cortical and subcortical brain-regions. APOE-e4 and MCI was also associated with higher cortical iron. Moreover, cerebral iron significantly affected functional coupling, and was furthermore associated with increased Aβ-plaque-load (R2-adjusted = 0.80, p < 0.001) and APOE-e4 carrier status (p < 0.001) in MCI. This study confirms earlier reports on an association between increased brain iron-burden and risk for neurocognitive dysfunction due to AD, and indicates that disease-progression is conferred by spatial colocalization of brain iron deposits with Aβ-plaques.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Amyloid beta-Peptides / metabolism*
  • Apolipoprotein E4 / genetics
  • Brain / metabolism*
  • Brain / pathology
  • Case-Control Studies
  • Cognitive Dysfunction / diagnostic imaging
  • Cognitive Dysfunction / metabolism*
  • Demography
  • Female
  • Heterozygote
  • Humans
  • Iron / metabolism*
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Organ Size
  • Positron-Emission Tomography
  • Prefrontal Cortex / metabolism
  • Prefrontal Cortex / pathology

Substances

  • Amyloid beta-Peptides
  • Apolipoprotein E4
  • Iron