APOE ϵ4 dose associates with increased brain iron and β-amyloid via blood-brain barrier dysfunction

Yuto Uchida, Hirohito Kan, Keita Sakurai, Yoshihiko Horimoto, Emi Hayashi, Akihiko Iida, Nobuyuki Okamura, Kenichi Oishi, Noriyuki Matsukawa

Research output: Contribution to journalArticlepeer-review

Abstract

Objective To examine the effect of apolipoprotein E (APOE) ϵ4 dose on blood-brain barrier (BBB) clearance function, evaluated using an advanced MRI technique and analyse its correlation with brain iron and β-amyloid accumulation in the early stages of the Alzheimer's continuum. Methods In this single-centre observational prospective cohort study, 24 APOE ϵ4 non-carriers, 22 heterozygotes and 20 homozygotes in the early stages of the Alzheimer's continuum were scanned with diffusion-prepared arterial spin labelling, which estimates the water exchange rate across the BBB (k w). Participants also underwent quantitative susceptibility mapping, [11 C]Pittsburgh compound B-positron emission tomography and neuropsychological testing. Using an atlas-based approach, we compared the regional k w of the whole brain among the groups and analysed its correlation with the neuroradiological and neuropsychological findings. Results The BBB k w values in the neocortices differed significantly among the groups (APOE ϵ4 non-carriers>heterozygotes>homozygotes). These values correlated with brain iron levels (frontal lobe: r=-0.476, 95% CI=-0.644 to-0.264, p=0.011; medial temporal lobe: r=-0.455, 95% CI=-0.628 to-0.239, p=0.017), β-amyloid loads (frontal lobe: r=-0.504, 95% CI=-0.731 to-0.176, p=0.015; medial temporal lobe: r=-0.452, 95% CI=-0.699 to-0.110, p=0.036) and neuropsychological scores, after adjusting for age, sex and APOE ϵ4 dose. Interpretation Our results suggest that an increased APOE ϵ4 dose is associated with decreased effective brain-waste clearance, such as iron and β-amyloid, through the BBB.

Original languageEnglish (US)
Pages (from-to)772-778
Number of pages7
JournalJournal of Neurology, Neurosurgery and Psychiatry
Volume93
Issue number7
DOIs
StatePublished - Jul 1 2022

Keywords

  • MRI
  • alzheimer's disease
  • blood-brain barrier

ASJC Scopus subject areas

  • Clinical Neurology
  • Psychiatry and Mental health
  • Surgery

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