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首页> 外文期刊>Stroke: A Journal of Cerebral Circulation >Amyloid-beta contributes to blood-brain barrier leakage in transgenic human amyloid precursor protein mice and in humans with cerebral amyloid angiopathy.
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Amyloid-beta contributes to blood-brain barrier leakage in transgenic human amyloid precursor protein mice and in humans with cerebral amyloid angiopathy.

机译：淀粉样蛋白β有助于转基因人类淀粉样蛋白前体蛋白小鼠和脑淀粉样血管病患者的血脑屏障渗漏。

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BACKGROUND AND PURPOSE: Cerebral amyloid angiopathy (CAA) is a degenerative disorder characterized by amyloid-beta (Abeta) deposition in the blood-brain barrier (BBB). CAA contributes to injuries of the neurovasculature including lobar hemorrhages, cortical microbleeds, ischemia, and superficial hemosiderosis. We postulate that CAA pathology is partially due to Abeta compromising the BBB. METHODS: We characterized 19 patients with acute stroke with "probable CAA" for neurovascular pathology based on MRI and clinical findings. Also, we studied the effect of Abeta on the expression of tight junction proteins and matrix metalloproteases (MMPs) in isolated rat brain microvessels. RESULTS: Two of 19 patients with CAA had asymptomatic BBB leakage and posterior reversible encephalopathic syndrome indicating increased BBB permeability. In addition to white matter changes, diffusion abnormality suggesting lacunar ischemia was found in 4 of 19 patients with CAA; superficial hemosiderosis was observed in 7 of 9 patients. Abeta(40) decreased expression of the tight junction proteins claudin-1 and claudin-5 and increased expression of MMP-2 and MMP-9. Analysis of brain microvessels from transgenic mice overexpressing human amyloid precursor protein revealed the same expression pattern for tight junction and MMP proteins. Consistent with reduced tight junction and increased MMP expression and activity, permeability was increased in brain microvessels from human amyloid precursor protein mice compared with microvessels from wild-type controls. CONCLUSIONS: Our findings indicate that Abeta contributes to changes in brain microvessel tight junction and MMP expression, which compromises BBB integrity. We conclude that Abeta causes BBB leakage and that assessing BBB permeability could potentially help characterize CAA progression and be a surrogate marker for treatment response.
机译：背景与目的：脑淀粉样血管病（CAA）是一种变性疾病，其特征是在血脑屏障（BBB）中沉积有淀粉样β（Abeta）。 CAA会导致神经血管损伤，包括大叶出血，皮质微出血，局部缺血和表皮铁血黄素沉着症。我们假设CAA病理部分归因于Abeta损害了BBB。方法：我们基于MRI和临床发现，对19例急性卒中患者进行了“可能的CAA”神经血管病理学检查。此外，我们研究了Abeta对分离大鼠脑微血管中紧密连接蛋白和基质金属蛋白酶（MMPs）表达的影响。结果：19例CAA患者中有2例无症状BBB漏出和后可逆性脑病综合征，表明BBB通透性增加。除白质改变外，在19例CAA患者中有4例发现弥散异常，提示腔隙性缺血。 9例患者中有7例出现表面含铁血黄素沉着病。 Abeta（40）减少紧密连接蛋白claudin-1和claudin-5的表达，并增加MMP-2和MMP-9的表达。分析过表达人淀粉样蛋白前体蛋白的转基因小鼠的大脑微血管，发现紧密连接蛋白和MMP蛋白表达模式相同。与减少的紧密连接和增加的MMP表达和活性相一致，与来自野生型对照的微血管相比，人淀粉样蛋白前体蛋白小鼠的脑微血管的通透性增加。结论：我们的发现表明，Abeta有助于大脑微血管紧密连接和MMP表达的改变，从而损害了血脑屏障的完整性。我们得出的结论是，Abeta会导致BBB渗漏，评估BBB的通透性可能有助于表征CAA进展，并成为治疗反应的替代指标。

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