APOE-ε4 selectively modulates posteromedial cortex activity during scene perception and short-term memory in young healthy adults

J P Shine, C J Hodgetts, M Postans, A D Lawrence, K S Graham

Research output: Contribution to journalArticlepeer-review


Apolipoprotein E (APOE) ε4 is a major genetic risk factor for Alzheimer's disease (AD), yet the mechanisms by which APOE-ε4 influences early-life brain function, and hence, in turn, risk for later-life AD, are poorly understood. Here, we report a novel, and selective, pattern of functional brain activity alteration in healthy young adult human APOE-ε4 carriers. Our findings suggest that APOE-ε4 may influence vulnerability to poorer later life cognitive health via its effect on posteromedial cortex (PMC), a hub region within a brain network involved in spatial processing, and necessary for episodic memory. In two neuroimaging tasks, APOE-ε4 carriers showed an inability to effectively modulate PMC during scene, but not face and object, working memory and perception. This striking pattern overlaps both functionally and topographically, with the earliest cognitive deficits seen in clinical AD, as well as reported alterations in the default network in amyloid-positive individuals at increased risk of AD.

Original languageEnglish
Article number16322
Pages (from-to)1-12
Number of pages12
JournalScientific Reports
Publication statusPublished - 10 Nov 2015


  • Alzheimer Disease/genetics
  • Apolipoprotein E4/genetics
  • Brain/diagnostic imaging
  • Cerebral Cortex/physiology
  • Female
  • Genotype
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Memory, Short-Term
  • Photic Stimulation
  • Polymorphism, Single Nucleotide
  • Radiography
  • Risk Factors
  • Visual Perception
  • Young Adult

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