APOE e4 dose associates with increased brain iron and β-amyloid via blood-brain barrier dysfunction
APOE e4 dose associates with increased brain iron and β-amyloid via blood-brain barrier dysfunction
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APOE e4 剂量通过血脑屏障功能障碍与脑铁和 β-淀粉样蛋白增加相关
DOI：
10.1136/jnnp-2021-328519
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发表时间：
2022
期刊：
影响因子：
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通讯作者：
Noriyuki Matsukawa
中科院分区：
文献类型：
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作者：
Yuto Uchida;Hirohito Kan;Keita Sakurai;Yoshihiko Horimoto;Emi Hayashi;Akihiko Iida;Nobuyuki Okamura;Kenichi Oishi;Noriyuki Matsukawa
目的探讨载脂蛋白Eɛ4剂量对阿尔茨海默病早期血脑屏障清除功能的影响，并分析其与脑内铁和β-淀粉样蛋白蓄积的相关性。方法在这项单中心观察的前瞻性队列研究中，用扩散法制备的动脉自旋标记扫描了24例非携带者、22例杂合子和20例纯合子阿尔茨海默病患者早期的血脑屏障，以估计跨血脑屏障的水交换率(Kw)。参与者还接受了定量易感图谱、[11C]匹兹堡化合物B正电子发射断层扫描和神经心理测试。采用基于图谱的方法，比较不同组间的全脑局部血流量，并分析其与神经放射学和神经心理学结果的相关性。结果不同组间的新皮质血脑屏障血流量差异有统计学意义(APOEɛ4non-carriers>；heterozygotes>；homozygotes).这些值与脑铁水平相关(额叶：R=−0.476，95%CI=−0.644至−0.264，p=0.011；内侧颞叶：R=−0.455，95% CI=−0.628至−0.239，p=0.017)，β-淀粉样蛋白负荷(额叶：R=−0.504，95% CI=−0.731至−0.176，p=0.015；内侧颞叶：r=−0.452，95% CI=−0.699至−0.110，p=0.036)和神经心理学评分，在调整了年龄、性别和APOEɛ4剂量后。解释我们的结果表明，APOEɛ4剂量增加与通过血脑屏障减少有效的脑废物清除有关，如铁和β-淀粉样蛋白。
ObjectiveTo examine the effect of apolipoprotein E (APOE)ɛ4dose 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, 24APOE ɛ4non-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 kwof the whole brain among the groups and analysed its correlation with the neuroradiological and neuropsychological findings.ResultsThe BBB kwvalues in the neocortices differed significantly among the groups (APOE ɛ4non-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 andAPOE ɛ4dose.InterpretationOur results suggest that an increasedAPOE ɛ4dose is associated with decreased effective brain-waste clearance, such as iron and β-amyloid, through the BBB.