title: APOE-ε4 selectively modulates posteromedial cortex activity during scene perception and short-term memory in young healthy adults.
abstract: 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.
authors.affiliation: School of Psychology and Cardiff University Brain Research Imaging Centre (CUBRIC), Cardiff University, UK, CF10 3AT.
authors.forename: J P
authors.initials: JP
authors.lastname: Shine
authors.affiliation: School of Psychology and Cardiff University Brain Research Imaging Centre (CUBRIC), Cardiff University, UK, CF10 3AT.
authors.forename: C J
authors.initials: CJ
authors.lastname: Hodgetts
authors.affiliation: School of Psychology and Cardiff University Brain Research Imaging Centre (CUBRIC), Cardiff University, UK, CF10 3AT.
authors.forename: M
authors.initials: M
authors.lastname: Postans
authors.affiliation: School of Psychology and Cardiff University Brain Research Imaging Centre (CUBRIC), Cardiff University, UK, CF10 3AT.
authors.forename: A D
authors.initials: AD
authors.lastname: Lawrence
authors.affiliation: School of Psychology and Cardiff University Brain Research Imaging Centre (CUBRIC), Cardiff University, UK, CF10 3AT.
authors.forename: K S
authors.initials: KS
authors.lastname: Graham
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics / Q000473:pathology; D053327:Apolipoprotein E4 / Q000235:genetics*; D001921:Brain / Q000000981:diagnostic imaging; D002540:Cerebral Cortex / Q000502:physiology*; D005260:Female; D005838:Genotype; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008570:Memory, Short-Term; D010775:Photic Stimulation; D020641:Polymorphism, Single Nucleotide; D011859:Radiography; D012307:Risk Factors; D014796:Visual Perception; D055815:Young Adult
chemical_list: D053327:Apolipoprotein E4