APOE4 moderates effects of cortical iron on synchronized default mode network activity in cognitively healthy old-aged adults

Sonja M. Kagerer, Jiri M.G. van Bergen, Xu Li, Frances C. Quevenco, Anton F. Gietl, Sandro Studer, Valerie Treyer, Rafael Meyer, Philipp A. Kaufmann, Roger M. Nitsch, Peter C.M. van Zijl, Christoph Hock, Paul G. Unschuld

Research output: Contribution to journalArticlepeer-review

6 Scopus citations


Introduction: Apolipoprotein E ε4 (APOE4)–related genetic risk for sporadic Alzheimer's disease is associated with an early impairment of cognitive brain networks. The current study determines relationships between APOE4 carrier status, cortical iron, and cortical network-functionality. Methods: Sixty-nine cognitively healthy old-aged individuals (mean age [SD] 66.1 [± 7.2] years; Mini-Mental State Exam [MMSE] 29.3 ± 1.1) were genotyped for APOE4 carrier-status and received 3 Tesla magnetic resonance imaging (MRI) for blood oxygen level–dependent functional magnetic resonance imaging (MRI) at rest, three-dimensional (3D)–gradient echo (six echoes) for cortical gray-matter, non-heme iron by quantitative susceptibility mapping, and 18F-flutemetamol positron emission tomography for amyloid-β. Results: A spatial pattern consistent with the default mode network (DMN) could be identified by independent component analysis. DMN activity was enhanced in APOE4 carriers and related to cortical iron burden. APOE4 and cortical iron synergistically interacted with DMN activity. Secondary analysis revealed a positive, APOE4 associated, relationship between cortical iron and DMN connectivity. Discussion: Our findings suggest that APOE4 moderates effects of iron on brain functionality prior to manifestation of cognitive impairment.

Original languageEnglish (US)
Article numbere12002
JournalAlzheimer's and Dementia: Diagnosis, Assessment and Disease Monitoring
Issue number1
StatePublished - Jan 2020


  • APOE4
  • DMN
  • ICA
  • MRI
  • PET
  • QSM
  • fMRI
  • flutemetamol
  • gradient echo
  • iron
  • preclinical Alzheimer's disease

ASJC Scopus subject areas

  • Clinical Neurology
  • Psychiatry and Mental health


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