近日，美国西奈山伊坎医学院Roland H. Friedel等研究人员合作发现，Plexin-B1对斑块周围胶质网中细胞间距的调控，影响阿尔茨海默病的胶质激活和淀粉样蛋白压实。相关论文于2024年5月27日发表在《自然—神经科学》杂志上。

研究人员揭示了反应性星形胶质细胞控制斑块周围胶质网中的细胞间距，从而限制微胶质细胞接触淀粉样蛋白沉积物。这一过程受导向受体Plexin-B1（PLXNB1）的控制，Plexin-B1是晚发性阿尔茨海默病（AD）患者的网络枢纽基因，在斑块相关星形胶质细胞中上调。在小鼠注意力缺失症模型中删除Plexin-B1，会导致斑块周围神经胶质网中反应性星形胶质细胞和小胶质细胞数量减少，但胶质过程对斑块的覆盖率增加，同时转录变化表明神经炎症减轻。

此外，胶质网足迹的减少与斑块总体负担的降低、向致密核心型斑块的转变以及神经营养不良的减少有关。总之，该研究证明，Plexin-B1可调节AD中斑块周围神经胶质网的激活。通过靶向引导受体放宽神经胶质间距可能是，增加斑块压实度和减少AD神经炎症的另一种策略。

据悉，神经胶质细胞之间的交流对AD的病理生理学有着深远的影响。

附：英文原文

Title: Regulation of cell distancing in peri-plaque glial nets by Plexin-B1 affects glial activation and amyloid compaction in Alzheimer’s disease

Author: Huang, Yong, Wang, Minghui, Ni, Haofei, Zhang, Jinglong, Li, Aiqun, Hu, Bin, Junqueira Alves, Chrystian, Wahane, Shalaka, Rios de Anda, Mitzy, Ho, Lap, Li, Yuhuan, Kang, Sangjo, Neff, Ryan, Kostic, Ana, Buxbaum, Joseph D., Crary, John F., Brennand, Kristen J., Zhang, Bin, Zou, Hongyan, Friedel, Roland H.

Issue&Volume: 2024-05-27

Abstract: Communication between glial cells has a profound impact on the pathophysiology of Alzheimer’s disease (AD). We reveal here that reactive astrocytes control cell distancing in peri-plaque glial nets, which restricts microglial access to amyloid deposits. This process is governed by guidance receptor Plexin-B1 (PLXNB1), a network hub gene in individuals with late-onset AD that is upregulated in plaque-associated astrocytes. Plexin-B1 deletion in a mouse AD model led to reduced number of reactive astrocytes and microglia in peri-plaque glial nets, but higher coverage of plaques by glial processes, along with transcriptional changes signifying reduced neuroinflammation. Additionally, a reduced footprint of glial nets was associated with overall lower plaque burden, a shift toward dense-core-type plaques and reduced neuritic dystrophy. Altogether, our study demonstrates that Plexin-B1 regulates peri-plaque glial net activation in AD. Relaxing glial spacing by targeting guidance receptors may present an alternative strategy to increase plaque compaction and reduce neuroinflammation in AD.

DOI: 10.1038/s41593-024-01664-w

Source: https://www.nature.com/articles/s41593-024-01664-w