Evidence of blood‐brain barrier permeability/leakage for circulating human Alzheimer's β‐amyloid‐(1–42)‐peptide
Evidence of blood‐brain barrier permeability/leakage for circulating human Alzheimer's β‐amyloid‐(1–42)‐peptide
复制标题
循环中的人阿尔茨海默病 β-淀粉样蛋白-(1-42)-肽血脑屏障渗透性/渗漏的证据
DOI：
10.1097/00001756-199605170-00008
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发表时间：
1996
期刊：
影响因子：
1.7
通讯作者：
A. Lipkowski
中科院分区：
文献类型：
--
作者：
R. Pluta;M. Barcikowska;S. Januszewski;A. Misicka;A. Lipkowski
阿尔茨海默病患者的脑含有淀粉样蛋白斑块，其由β-淀粉样蛋白肽组成，被认为在该疾病的神经病理学中起因果作用。阿尔茨海默病患者脑实质和血管中β-淀粉样肽的来源尚不清楚。本研究检查了大鼠血脑屏障对β-淀粉样蛋白肽的渗透性，这些大鼠接受单次或重复全脑缺血，然后静脉注射人合成β-淀粉样蛋白-（1-42）-肽。在缺血后接受β-淀粉样肽的大鼠表现出β-淀粉样肽在海马、大脑皮质中的多灶性和广泛蓄积，偶尔在白色物质中蓄积。β-淀粉样肽渗透累及小动脉、静脉和微静脉。神经元、胶质细胞和周细胞体充满β-淀粉样肽。因此，首次提供了可溶性人β-淀粉样蛋白-（1-42）-肽穿过血脑屏障并从循环进入大脑的直接证据。
BRAINS from patients with Alzheimer's disease contain amyloid plaques which are composed of β-amyloid peptide and are considered to play a causal role in the neuropathology of this disease. The origin of β-amyloid peptide in brain parenchyma and vessels of Alzheimer's disease patients is not known. This study examined the permeability of the blood-brain barrier to β-amyloid peptide in rats subjected to single or repeated episodes of global cerebral ischaemia followed by i.v. injections of human synthetic β-amyloid-(1–42)-peptide. Rats receiving β-amyloid peptide after ischaemia demonstrated multifocal and widespread accumulation of β-amyloid peptide in hippocampus, cerebral cortex and occasionally in white matter. β-Amyloid peptide penetration involved arterioles, veins and venules. Neuronal, glial and pericyte bodies were observed filled with β-amyloid peptide. Direct evidence that soluble human β-amyloid-(1–42)-peptide crosses the blood-brain barrier and enters the brain from the circulation is thus provided for the first time.