小胶质细胞使用TAM受体感知和吞噬β淀粉样蛋白斑块，这一成果由美国索克生物研究所Greg Lemke课题组经过不懈努力而取得。 这一研究成果于2021年4月15日发表在国际学术期刊《自然-免疫学》上。

研究人员发现在阿尔茨海默氏病及其小鼠模型中，淀粉样蛋白相关小胶质细胞中Axl和Mer的诱导表达与TAM配体Gas6及其共配体磷脂酰丝氨酸诱导的斑块修饰相关。 在阿尔茨海默氏病相病APP/PS1小鼠模型中，Axl和Mer基因缺失会导致小胶质细胞无法正常感知、应答、组织或吞噬淀粉样β斑块。尽管存在这些缺陷，但TAM缺失的APP/PS1小鼠比含有APP / PS1正常小胶质细胞的小鼠产生更少的致密斑。

该发现表明，TAM是小胶质细胞识别和吞噬淀粉样蛋白斑块所必不可少的媒介，并且TAM介导的小胶质细胞吞噬作用会促进而非抑制致密斑块的形成。

据了解，已知两种小胶质TAM受体酪氨酸激酶Axl和Mer与阿尔茨海默氏病相关，但尚未利用实验测试它们在疾病中的作用。

附：英文原文

Title: Microglia use TAM receptors to detect and engulf amyloid β plaques

Author: Youtong Huang, Kaisa E. Happonen, Patrick G. Burrola, Carolyn OConnor, Nasun Hah, Ling Huang, Axel Nimmerjahn, Greg Lemke

Issue&Volume: 2021-04-15

Abstract: Two microglial TAM receptor tyrosine kinases, Axl and Mer, have been linked to Alzheimer’s disease, but their roles in disease have not been tested experimentally. We find that in Alzheimer’s disease and its mouse models, induced expression of Axl and Mer in amyloid plaque–associated microglia was coupled to induced plaque decoration by the TAM ligand Gas6 and its co-ligand phosphatidylserine. In the APP/PS1 mouse model of Alzheimer’s disease, genetic ablation of Axl and Mer resulted in microglia that were unable to normally detect, respond to, organize or phagocytose amyloid-β plaques. These major deficits notwithstanding, TAM-deficient APP/PS1 mice developed fewer dense-core plaques than APP/PS1 mice with normal microglia. Our findings reveal that the TAM system is an essential mediator of microglial recognition and engulfment of amyloid plaques and that TAM-driven microglial phagocytosis does not inhibit, but rather promotes, dense-core plaque development.

DOI: 10.1038/s41590-021-00913-5

Source: https://www.nature.com/articles/s41590-021-00913-5