Uchida Yuto, Kan Hirohito, Sakurai Keita, Horimoto Yoshihiko, Hayashi Emi, Iida Akihiko, Okamura Nobuyuki, Oishi Kenichi, Matsukawa Noriyuki
Department of Neurology, Nagoya City University, Nagoya, Japan.
Department of Neurology, Toyokawa City Hospital, Toyokawa, Japan.
J Neurol Neurosurg Psychiatry. 2022 Apr 28. doi: 10.1136/jnnp-2021-328519.
To examine the effect of apolipoprotein E () 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.
In this single-centre observational prospective cohort study, 24 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). Participants also underwent quantitative susceptibility mapping, [C]Pittsburgh compound B-positron emission tomography and neuropsychological testing. Using an atlas-based approach, we compared the regional k of the whole brain among the groups and analysed its correlation with the neuroradiological and neuropsychological findings.
The BBB k values in the neocortices differed significantly among the groups ( non-carriers>heterozygotes>homozygotes). These values correlated with brain iron levels (frontal lobe: =-0.476, 95% CI=-0.644 to -0.264, p=0.011; medial temporal lobe: =-0.455, 95% CI=-0.628 to -0.239, p=0.017), β-amyloid loads (frontal lobe: =-0.504, 95% CI=-0.731 to -0.176, p=0.015; medial temporal lobe: =-0.452, 95% CI=-0.699 to -0.110, p=0.036) and neuropsychological scores, after adjusting for age, sex and dose.
Our results suggest that an increased dose is associated with decreased effective brain-waste clearance, such as iron and β-amyloid, through the BBB.
使用先进的磁共振成像（MRI）技术检测载脂蛋白E（apoE）剂量对血脑屏障（BBB）清除功能的影响，并分析其与阿尔茨海默病连续体早期脑铁和β淀粉样蛋白积累的相关性。
在这项单中心观察性前瞻性队列研究中，对24名阿尔茨海默病连续体早期的apoE非携带者、22名杂合子和20名纯合子进行了扩散准备动脉自旋标记扫描，该扫描可估计水通过血脑屏障的交换率（k）。参与者还接受了定量磁化率映射、[C]匹兹堡化合物B正电子发射断层扫描和神经心理学测试。我们采用基于图谱的方法，比较了各组全脑的区域k值，并分析了其与神经放射学和神经心理学结果的相关性。
各组新皮质中的血脑屏障k值存在显著差异（apoE非携带者>杂合子>纯合子）。在调整年龄、性别和apoE剂量后，这些值与脑铁水平（额叶：r = -0.476，95%置信区间=-0.644至-0.264，p = 0.011；内侧颞叶：r = -0.455，95%置信区间=-0.628至-0.239，p = 0.017）、β淀粉样蛋白负荷（额叶：r = -0.504，95%置信区间=-0.731至-0.176，p = 0.015；内侧颞叶：r = -0.452，95%置信区间=-0.699至-0.110，p = 0.036）和神经心理学评分相关。
我们的结果表明，apoE剂量增加与通过血脑屏障清除脑内铁和β淀粉样蛋白等有效脑废物的能力降低有关。
