title: Reduced cerebrovascular reactivity in young adults carrying the APOE ε4 allele.
abstract: BACKGROUND
  Functional magnetic resonance imaging (MRI) studies have shown that APOE ε2- and ε4-carriers have similar patterns of blood-oxygenation-level-dependent (BOLD) activation suggesting that we need to look beyond the BOLD signal to link APOE's effect on the brain to Alzheimer's disease (AD)-risk.
  
  
  METHODS
  We evaluated APOE-related differences in BOLD activation in response to a memory task, cerebrovascular reactivity using a CO2-inhalation challenge (CO2-CVR), and the potential contribution of CO2-CVR to the BOLD signal.
  
  
  RESULTS
  APOE ε4-carriers had the highest task-related hippocampal BOLD signal relative to non-carriers. The largest differences in CO2-CVR were between ε2- and ε4-carriers, with the latter having the lowest values. Genotype differences in CO2-CVR accounted for ∼70% of hippocampal BOLD differences between groups.
  
  
  CONCLUSIONS
  Because CO2-CVR gauges vascular health, the differential effect of APOE in young adults may reflect a vascular contribution to the vulnerability of ε4-carriers to late-life pathology. Studies confirming our findings are warranted.
authors.affiliation: Department of Psychiatry, University of Oxford, Oxford United Kingdom; Functional Magnetic Resonance Imaging of the Brain Centre, University of Oxford, Oxford United Kingdom.
authors.forename: Sana
authors.initials: S
authors.lastname: Suri
authors.affiliation: Department of Psychiatry, University of Oxford, Oxford United Kingdom; Functional Magnetic Resonance Imaging of the Brain Centre, University of Oxford, Oxford United Kingdom.
authors.forename: Clare E
authors.initials: CE
authors.lastname: Mackay
authors.affiliation: Functional Magnetic Resonance Imaging of the Brain Centre, University of Oxford, Oxford United Kingdom.
authors.forename: Michael E
authors.initials: ME
authors.lastname: Kelly
authors.affiliation: Functional Magnetic Resonance Imaging of the Brain Centre, University of Oxford, Oxford United Kingdom.
authors.forename: Michael
authors.initials: M
authors.lastname: Germuska
authors.affiliation: Department of Psychiatry, University of Oxford, Oxford United Kingdom.
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: Tunbridge
authors.affiliation: Laboratory of Epidemiology, Neuroimaging, and Telemedicine, Istituto di Ricovero e Cura a Carattere Scientifico San Giovanni di Dio-Fatebenefratelli, Brescia, Italy; Department of Psychiatry, University Hospital and University of Geneva, Chene-Bourg, Switzerland.
authors.forename: Giovanni B
authors.initials: GB
authors.lastname: Frisoni
authors.affiliation: Division of Brain Sciences, Imperial College, Hammersmith Campus London, United Kingdom.
authors.forename: Paul M
authors.initials: PM
authors.lastname: Matthews
authors.affiliation: Department of Psychiatry, University of Oxford, Oxford United Kingdom.
authors.forename: Klaus P
authors.initials: KP
authors.lastname: Ebmeier
authors.affiliation: Functional Magnetic Resonance Imaging of the Brain Centre, University of Oxford, Oxford United Kingdom.
authors.forename: Daniel P
authors.initials: DP
authors.lastname: Bulte
authors.affiliation: Department of Psychiatry, University of Oxford, Oxford United Kingdom; Functional Magnetic Resonance Imaging of the Brain Centre, University of Oxford, Oxford United Kingdom. Electronic address: nicolaf@fmrib.ox.ac.uk.
authors.forename: Nicola
authors.initials: N
authors.lastname: Filippini
mesh_terms: D000328:Adult; D053327:Apolipoprotein E4 / Q000235:genetics*; D001921:Brain / Q000502:physiology*; D001931:Brain Mapping; D002245:Carbon Dioxide / Q000378:metabolism; D002560:Cerebrovascular Circulation / Q000502:physiology*; D005260:Female; D005838:Genotype; D006579:Heterozygote; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D009483:Neuropsychological Tests; D010100:Oxygen / Q000097:blood; D010364:Pattern Recognition, Visual / Q000502:physiology; D021641:Recognition, Psychology / Q000502:physiology; D055815:Young Adult
chemical_list: D053327:Apolipoprotein E4; D002245:Carbon Dioxide; D010100:Oxygen
keywords: APOE gene; Alzheimer's disease; BOLD; Cerebrovascular reactivity; fMRI