TY - JOUR
T1 - APOE ϵ4 dose associates with increased brain iron and β-amyloid via blood-brain barrier dysfunction
AU - Uchida, Yuto
AU - Kan, Hirohito
AU - Sakurai, Keita
AU - Horimoto, Yoshihiko
AU - Hayashi, Emi
AU - Iida, Akihiko
AU - Okamura, Nobuyuki
AU - Oishi, Kenichi
AU - Matsukawa, Noriyuki
N1 - Publisher Copyright:
©
PY - 2022/7/1
Y1 - 2022/7/1
N2 - 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.
AB - 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.
KW - MRI
KW - alzheimer's disease
KW - blood-brain barrier
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U2 - 10.1136/jnnp-2021-328519
DO - 10.1136/jnnp-2021-328519
M3 - Article
C2 - 35483916
AN - SCOPUS:85130834175
SN - 0022-3050
VL - 93
SP - 772
EP - 778
JO - Journal of Neurology, Neurosurgery and Psychiatry
JF - Journal of Neurology, Neurosurgery and Psychiatry
IS - 7
ER -