Complement and microglia mediate early synapse loss in Alzheimer mouse models.
Complement and microglia mediate early synapse loss in Alzheimer mouse models.
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DOI：
10.1126/science.aad8373
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发表时间：
2016-05-06
期刊：
影响因子：
--
通讯作者：
Stevens B
中科院分区：
文献类型：
--
作者：
Hong S;Beja-Glasser VF;Nfonoyim BM;Frouin A;Li S;Ramakrishnan S;Merry KM;Shi Q;Rosenthal A;Barres BA;Lemere CA;Selkoe DJ;Stevens B
阿尔茨海默病（AD）中的突触丢失与认知能力下降相关。AD中小胶质细胞和补体的参与归因于神经炎症，在疾病晚期突出。在这里，我们在小鼠模型中显示，补体和小胶质细胞介导的突触损失早期AD。C1 q是经典补体级联反应的起始蛋白，在明显斑块沉积之前增加并与突触相关。抑制C1 q、C3或小胶质细胞补体受体CR 3可减少吞噬性小胶质细胞的数量以及早期突触丢失的程度。C1 q是可溶性β-淀粉样蛋白（Aβ）寡聚体对突触和海马长时程增强（LTP）的毒性作用所必需的。最后，当暴露于可溶性Aβ寡聚体时，成人脑中的小胶质细胞在CR 3依赖性过程中吞噬突触物质。总之，这些研究结果表明，补体依赖性途径和小胶质细胞修剪多余的突触在发展中不适当地激活和介导的突触损失在AD。
Synapse loss in Alzheimer's disease (AD) correlates with cognitive decline. Involvement of microglia and complement in AD has been attributed to neuroinflammation, prominent late in disease. Here we show in mouse models that complement and microglia mediate synaptic loss early in AD. C1q, the initiating protein of the classical complement cascade, is increased and associated with synapses before overt plaque deposition. Inhibition of C1q, C3 or the microglial complement receptor CR3, reduces the number of phagocytic microglia as well as the extent of early synapse loss. C1q is necessary for the toxic effects of soluble β-amyloid (Aβ) oligomers on synapses and hippocampal long-term potentiation (LTP). Finally, microglia in adult brains engulf synaptic material in a CR3-dependent process when exposed to soluble Aβ oligomers. Together, these findings suggest that the complement-dependent pathway and microglia that prune excess synapses in development are inappropriately activated and mediate synapse loss in AD.
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影响因子：
5.4
作者：
Wyss-Coray, Tony;Rogers, Joseph
通讯作者：
Rogers, Joseph
影响因子：
56.9
作者：
Selkoe, DJ
通讯作者：
Selkoe, DJ
影响因子：
16.2
作者：
Datwani, Akash;McConnell, Michael J.;Kanold, Patrick O.;Micheva, Kristina D.;Busse, Brad;Shamloo, Mehrdad;Smith, Stephen J.;Shatz, Carla J.
通讯作者：
Shatz, Carla J.
DOI：
10.1523/jneurosci.5341-09.2010
发表时间：
2010-01-06
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Harris JA;Devidze N;Halabisky B;Lo I;Thwin MT;Yu GQ;Bredesen DE;Masliah E;Mucke L
通讯作者：
Mucke L
影响因子：
11.2
作者：
TERRY, RD;MASLIAH, E;KATZMAN, R
通讯作者：
KATZMAN, R