Distinct patterns of brain activity in young carriers of the APOE-ε4 allele

Nicola Filippini, Bradley J. MacIntosh, Morgan G. Hough, Guy M. Goodwin, Giovanni B. Frisoni, Stephen M. Smith, Paul M. Matthews, Christian F. Beckmann, Clare E. Mackay

Research output: Contribution to journalArticlepeer-review


The APOE ε4 allele isa risk factor for late-life pathological changes that is also associated with anatomical and functional brain changes in middle-aged and elderly healthy subjects. We investigated structural and functional effects of the APOE polymorphism in 18 young healthy APOE ε4-carriers and 18 matched noncarriers (age range: 20-35 years). Brain activity was studied both at rest and during an encoding memory paradigm using blood oxygen level-dependent fMRI. Resting fMRI revealed increased "default mode network" (involving retrosplenial, medial temporal, and medial-pref rontal cortical areas) coactivation in ε4-carriers relative to noncarriers. The encoding task produced greater hippocampal activation in ε4-carriers relative to noncarriers. Neither result could be explained by differences in memory performance, brain morphology, or resting cerebral blood flow. The APOE ε4 allele modulates brain function decades before any clinical or neuro-physiological expression of neurodegenerative processes.

Original languageEnglish
Pages (from-to)7209-7214
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number17
Publication statusPublished - Apr 28 2009


  • Hippocampus
  • Memory
  • Neuroimaging
  • Resting connectivity

ASJC Scopus subject areas

  • General


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