Gram-negative bacterial molecules associate with Alzheimer disease pathology.
Gram-negative bacterial molecules associate with Alzheimer disease pathology.
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DOI：
10.1212/wnl.0000000000003391
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发表时间：
2016-11-29
期刊：
影响因子：
9.9
通讯作者：
Sharp FR
中科院分区：
文献类型：
--
作者：
Zhan X;Stamova B;Jin LW;DeCarli C;Phinney B;Sharp FR
我们确定了革兰氏阴性细菌分子是否与阿尔茨海默病（AD）神经病理学相关，因为先前的研究表明革兰氏阴性大肠杆菌细菌可以形成细胞外淀粉样蛋白，并且革兰氏阴性细菌已被报道为正常人脑中发现的主要细菌。研究了AD患者（n = 24）和年龄匹配对照组（n = 18）的灰质和白色物质脑样本。Western印迹和免疫细胞化学法检测细胞内脂多糖（LPS）和大肠杆菌K99皮利蛋白。评估人脑样品的大肠杆菌DNA，然后进行DNA测序。LPS和大肠杆菌K99在所有AD和对照组的脑实质和血管中被免疫细胞化学检测到。与对照脑相比，使用蛋白质印迹测量的K99水平在AD中更高（p < 0.01），并且K99定位于AD中的神经元样细胞，而不是对照脑。与对照组相比，AD组的LPS水平也更高。LPS与Aβ1-40/42共定位于淀粉样斑块中，与Aβ1-40/42共定位于AD脑中的血管周围。DNA测序证实了人类对照和AD大脑中的大肠杆菌DNA。AD患者的大肠杆菌K99和LPS水平高于对照组。LPS与Aβ1-40/42共定位于AD脑内的淀粉样斑块和血管周围。数据显示革兰氏阴性细菌分子与AD神经病理学相关。它们与我们的LPS-缺血-缺氧大鼠模型一致，该模型产生与Aβ共定位并类似于淀粉样斑块的髓鞘聚集体。
We determined whether Gram-negative bacterial molecules are associated with Alzheimer disease (AD) neuropathology given that previous studies demonstrate Gram-negative Escherichia coli bacteria can form extracellular amyloid and Gram-negative bacteria have been reported as the predominant bacteria found in normal human brains. Brain samples from gray and white matter were studied from patients with AD (n = 24) and age-matched controls (n = 18). Lipopolysaccharide (LPS) and E coli K99 pili protein were evaluated by Western blots and immunocytochemistry. Human brain samples were assessed for E coli DNA followed by DNA sequencing. LPS and E coli K99 were detected immunocytochemically in brain parenchyma and vessels in all AD and control brains. K99 levels measured using Western blots were greater in AD compared to control brains (p < 0.01) and K99 was localized to neuron-like cells in AD but not control brains. LPS levels were also greater in AD compared to control brain. LPS colocalized with Aβ1-40/42 in amyloid plaques and with Aβ1-40/42 around vessels in AD brains. DNA sequencing confirmed E coli DNA in human control and AD brains. E coli K99 and LPS levels were greater in AD compared to control brains. LPS colocalized with Aβ1-40/42 in amyloid plaques and around vessels in AD brain. The data show that Gram-negative bacterial molecules are associated with AD neuropathology. They are consistent with our LPS-ischemia-hypoxia rat model that produces myelin aggregates that colocalize with Aβ and resemble amyloid-like plaques.