Lipopolysaccharide Associates with Amyloid Plaques, Neurons and Oligodendrocytes in Alzheimer's Disease Brain: A Review.
Lipopolysaccharide Associates with Amyloid Plaques, Neurons and Oligodendrocytes in Alzheimer's Disease Brain: A Review.
复制标题
DOI：
10.3389/fnagi.2018.00042
复制
发表时间：
2018
影响因子：
4.8
通讯作者：
Sharp FR
中科院分区：
文献类型：
--
作者：
Zhan X;Stamova B;Sharp FR
本文综述了脂多糖（LPS，发现在所有革兰氏阴性菌的壁）可能在引起散发性阿尔茨海默病（AD）中发挥作用。这部分是基于最近的研究表明：革兰氏阴性E。大肠杆菌可形成细胞外淀粉样蛋白;细菌编码的16 S rRNA存在于所有人脑中，超过70%为革兰氏阴性菌;超微结构分析显示AD患者红细胞中存在微生物; AD患者血液LPS水平是对照组的3倍; LPS结合局灶性脑缺血和缺氧在成年大鼠皮层产生淀粉样蛋白样斑块和髓鞘损伤。此外，革兰氏阴性细菌LPS被发现在老化对照组和AD脑中，虽然LPS水平在AD脑中高得多。此外，脂多糖与淀粉样斑块，血管周围淀粉样蛋白，神经元和少突胶质细胞在AD脑共定位。基于LPS引起少突胶质细胞损伤的假设，发现AD中降解的髓鞘碱性蛋白（dMBP）水平比对照脑高得多。免疫荧光显示，AD脑内淀粉样斑块中dMBP与β淀粉样蛋白（Aβ）和LPS共定位，室周白色物质（WM）中dMBP与其他髓鞘分子共定位于囊泡壁。这些数据导致了这样的假设，即LPS作用于白细胞和小胶质细胞TLR 4-CD 14/TLR 2受体以产生NF κ B介导的细胞因子增加，其增加Aβ水平，损伤少突胶质细胞并产生AD脑中发现的髓鞘损伤。由于Aβ1-42也是TLR 4受体的激动剂，这可能会产生恶性循环，导致AD的持续进展。因此，LPS、TLR 4受体复合物和革兰氏阴性菌可能是散发性AD的治疗或预防靶点。
This review proposes that lipopolysaccharide (LPS, found in the wall of all Gram-negative bacteria) could play a role in causing sporadic Alzheimer’s disease (AD). This is based in part upon recent studies showing that: Gram-negative E. coli bacteria can form extracellular amyloid; bacterial-encoded 16S rRNA is present in all human brains with over 70% being Gram-negative bacteria; ultrastructural analyses have shown microbes in erythrocytes of AD patients; blood LPS levels in AD patients are 3-fold the levels in control; LPS combined with focal cerebral ischemia and hypoxia produced amyloid-like plaques and myelin injury in adult rat cortex. Moreover, Gram-negative bacterial LPS was found in aging control and AD brains, though LPS levels were much higher in AD brains. In addition, LPS co-localized with amyloid plaques, peri-vascular amyloid, neurons, and oligodendrocytes in AD brains. Based upon the postulate LPS caused oligodendrocyte injury, degraded Myelin Basic Protein (dMBP) levels were found to be much higher in AD compared to control brains. Immunofluorescence showed that the dMBP co-localized with β amyloid (Aβ) and LPS in amyloid plaques in AD brain, and dMBP and other myelin molecules were found in the walls of vesicles in periventricular White Matter (WM). These data led to the hypothesis that LPS acts on leukocyte and microglial TLR4-CD14/TLR2 receptors to produce NFkB mediated increases of cytokines which increase Aβ levels, damage oligodendrocytes and produce myelin injury found in AD brain. Since Aβ1–42 is also an agonist for TLR4 receptors, this could produce a vicious cycle that accounts for the relentless progression of AD. Thus, LPS, the TLR4 receptor complex, and Gram-negative bacteria might be treatment or prevention targets for sporadic AD.
登录
查看更多内容
影响因子：
3.1
作者：
de Haas, CJC;van Leeuwen, EMM;van Strijp, JAG
通讯作者：
van Strijp, JAG
影响因子：
2.1
作者：
Bai Z;Stamova B;Xu H;Ander BP;Wang J;Jickling GC;Zhan X;Liu D;Han G;Jin LW;DeCarli C;Lei H;Sharp FR
通讯作者：
Sharp FR
影响因子：
6
作者：
Desai, Maya K.;Mastrangelo, Michael A.;Bowers, William J.
通讯作者：
Bowers, William J.
影响因子：
--
作者：
Deng, Wenbin;Pleasure, Jeanette;Pleasure, David
通讯作者：
Pleasure, David
影响因子：
4.2
作者：
Bartzokis G
通讯作者：
Bartzokis G