APOE ɛ4剂量通过血脑屏障功能障碍导致脑铁和β-淀粉样蛋白增加。

IF 0.5 4区哲学 Q3 HISTORY & PHILOSOPHY OF SCIENCE

Endeavour Pub Date : 2022-04-28 DOI:10.1136/jnnp-2021-328519

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

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引用次数: 0

摘要

目的利用先进的磁共振成像技术评估载脂蛋白E（APOE）ɛ4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氏症早期脑铁和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，24 名 APOE ɛ4 非携带者、22 名杂合基因携带者和 20 名同种基因携带者在阿尔茨海默氏症的早期阶段接受了弥散预处理动脉自旋标记扫描，该技术可估算跨 BBB 的水交换率（kw）。参与者还接受了定量易感图、[11C]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，比较了各组间全脑区域的 kw 值，并分析了其与神经放射学和神经心理学结果的相关性：结果：各组（APOE ɛ4非携带者>杂合子>高杂合子）新皮质中的BBB kw值差异显著。这些值与脑铁水平（额叶：r=-0.476，95% CI=-0.644至-0.264，p=0.011；颞叶内侧：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，然后调整年龄、性别和APOEɛ4剂量：我们的研究结果表明，APOE ɛ4剂量的增加与铁和β-淀粉样蛋白等脑废物通过BBB的有效清除率降低有关。

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APOE ɛ4 dose associates with increased brain iron and β-amyloid via blood-brain barrier dysfunction.

Objective: To 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.

Methods: In 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 (k_w). 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 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 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.

Interpretation: Our 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.

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来源期刊

Endeavour 综合性期刊-科学史与科学哲学

CiteScore

1.10

自引率

16.70%

发文量

审稿时长

49 days

期刊介绍： Endeavour, established in 1942, has, over its long and proud history, developed into one of the leading journals in the history and philosophy of science. Endeavour publishes high-quality articles on a wide array of scientific topics from ancient to modern, across all disciplines. It serves as a critical forum for the interdisciplinary exploration and evaluation of natural knowledge and its development throughout history. Each issue contains lavish color and black-and-white illustrations. This makes Endeavour an ideal destination for history and philosophy of science articles with a strong visual component. Endeavour presents the history and philosophy of science in a clear and accessible manner, ensuring the journal is a valuable tool for historians, philosophers, practicing scientists, and general readers. To enable it to have the broadest coverage possible, Endeavour features four types of articles: -Research articles are concise, fully referenced, and beautifully illustrated with high quality reproductions of the most important source material. -In Vivo articles will illustrate the rich and numerous connections between historical and philosophical scholarship and matters of current public interest, and provide rich, readable explanations of important current events from historical and philosophical perspectives. -Book Reviews and Commentaries provide a picture of the rapidly growing history of science discipline. Written by both established and emerging scholars, our reviews provide a vibrant overview of the latest publications and media in the history and philosophy of science. -Lost and Found Pieces are playful and creative short essays which focus on objects, theories, tools, and methods that have been significant to science but underappreciated by collective memory.