• Yuto Uchida, Hirohito Kan, Keita Sakurai, Yoshihiko Horimoto, Emi Hayashi, Akihiko Iida, Nobuyuki Okamura, Kenichi Oishi, and Noriyuki Matsukawa.
• Department of Neurology, Nagoya City University, Nagoya, Japan.
• J. Neurol. Neurosurg. Psychiatr. 2022 Apr 28.

ObjectiveTo examine the effect of apolipoprotein E (APOE) ɛ4 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.MethodsIn this single-centre observational prospective cohort study, 24 APOE ɛ4 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 (kw). Participants also underwent quantitative susceptibility mapping, [11C]Pittsburgh compound B-positron emission tomography and neuropsychological testing. Using an atlas-based approach, we compared the regional kw of the whole brain among the groups and analysed its correlation with the neuroradiological and neuropsychological findings.ResultsThe BBB kw values in the neocortices differed significantly among the groups (APOE ɛ4 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 ɛ4 dose.InterpretationOur results suggest that an increased APOE ɛ4 dose is associated with decreased effective brain-waste clearance, such as iron and β-amyloid, through the BBB.© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.

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