美国圣路易斯华盛顿大学
研究人员描述了一种表达人类载脂蛋白亚型的tau病理基因工程小鼠模型，科在无菌条件下或用抗生素扰乱其肠道微生物群后饲养。这两种操作都以性别和载脂蛋白亚型依赖的方式减少了胶质增生、tau病理和神经退行性。这些发现揭示了微生物群、神经炎症和tau介导的神经退行性之间的机制和翻译相关的相互关系。
据悉，tau介导的神经退行性变是阿尔茨海默病的一个标志。原发性tau病理的特征是病理性tau积累和神经元和突触损失。载脂蛋白E（ApoE）介导的神经炎症参与了tau介导的神经退行性变的进展，新出现的证据表明，肠道微生物群以一种依赖于ApoE基因型的方式调节神经炎症。然而，缺乏证据表明微生物群和tau介导的神经退行性变之间的因果关系。
附：英文原文
Title: ApoE isoform– and microbiota-dependent progression of neurodegeneration in a mouse model of tauopathy
Author: Dong-oh Seo, David O’Donnell, Nimansha Jain, Jason D. Ulrich, Jasmin Herz, Yuhao Li, Mackenzie Lemieux, Jiye Cheng, Hao Hu, Javier R. Serrano, Xin Bao, Emily Franke, Maria Karlsson, Martin Meier, Su Deng, Chandani Desai, Hemraj Dodiya, Janaki Lelwala-Guruge, Scott A. Handley, Jonathan Kipnis, Sangram S. Sisodia, Jeffrey I. Gordon, David M. Holtzman
Issue&Volume: 2023-01-13
Abstract: Tau-mediated neurodegeneration is a hallmark of Alzheimer’s disease. Primary tauopathies are characterized by pathological tau accumulation and neuronal and synaptic loss. Apolipoprotein E (ApoE)–mediated neuroinflammation is involved in the progression of tau-mediated neurodegeneration, and emerging evidence suggests that the gut microbiota regulates neuroinflammation in an APOE genotype–dependent manner. However, evidence of a causal link between the microbiota and tau-mediated neurodegeneration is lacking. In this study, we characterized a genetically engineered mouse model of tauopathy expressing human ApoE isoforms reared under germ-free conditions or after perturbation of their gut microbiota with antibiotics. Both of these manipulations reduced gliosis, tau pathology, and neurodegeneration in a sex- and ApoE isoform–dependent manner. The findings reveal mechanistic and translationally relevant interrelationships between the microbiota, neuroinflammation, and tau-mediated neurodegeneration.
DOI: add1236
Source: https://www.science.org/doi/10.1126/science.add1236