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小胶质细胞的激活和tau在Braak阶段共同传播
作者:小柯机器人 发布时间:2021/8/29 16:01:01

加拿大麦吉尔大学Pedro Rosa-Neto、美国匹兹堡大学Tharick A. Pascoal等研究人员合作发现,小胶质细胞的激活和tau在Braak阶段共同传播。相关论文于2021年8月26日在线发表在《自然—医学》杂志上。

大量实验证据表明,小胶质细胞的激活参与了阿尔茨海默病(AD)中tau缠结在新皮层的传播。研究人员测试了一种假设,即小胶质细胞激活的空间传播和tau的积累在活体人脑中以类似Braak的模式共同定位。研究人员用正电子发射断层扫描脑成像技术研究了130个不同衰老和AD临床谱系的个体,用于检测小胶质细胞激活([11C]PBR28)、淀粉样β(Aβ)([18F]AZD4694)和tau([18F]MK-6240)病理。研究人员进一步评估了表达在骨髓细胞上的小胶质触发受体2(TREM2)脑脊液(CSF)的浓度和大脑基因表达模式。研究人员发现,[11C]PBR28与CSF可溶性TREM2相关,并显示出与TREM2基因表达相似的区域分布。

网络分析显示,小胶质细胞的激活和tau在Braak样阶段后相互间有层次性的关联。回归分析显示,纵向的tau传播途径取决于基线小胶质细胞网络而不是tau网络回路。在这些研究人群中,Aβ、tau和小胶质细胞异常的共同出现是预测认知障碍的最强因素。这项研究结果支持一种模型,即Aβ和激活的小胶质细胞之间的互动为tau在Braak阶段的传播设定了节奏。

附:英文原文

Title: Microglial activation and tau propagate jointly across Braak stages

Author: Pascoal, Tharick A., Benedet, Andrea L., Ashton, Nicholas J., Kang, Min Su, Therriault, Joseph, Chamoun, Mira, Savard, Melissa, Lussier, Firoza Z., Tissot, Ccile, Karikari, Thomas K., Ottoy, Julie, Mathotaarachchi, Sulantha, Stevenson, Jenna, Massarweh, Gassan, Schll, Michael, de Leon, Mony J., Soucy, Jean-Paul, Edison, Paul, Blennow, Kaj, Zetterberg, Henrik, Gauthier, Serge, Rosa-Neto, Pedro

Issue&Volume: 2021-08-26

Abstract: Compelling experimental evidence suggests that microglial activation is involved in the spread of tau tangles over the neocortex in Alzheimer’s disease (AD). We tested the hypothesis that the spatial propagation of microglial activation and tau accumulation colocalize in a Braak-like pattern in the living human brain. We studied 130 individuals across the aging and AD clinical spectrum with positron emission tomography brain imaging for microglial activation ([11C]PBR28), amyloid-β (Aβ) ([18F]AZD4694) and tau ([18F]MK-6240) pathologies. We further assessed microglial triggering receptor expressed on myeloid cells 2 (TREM2) cerebrospinal fluid (CSF) concentrations and brain gene expression patterns. We found that [11C]PBR28 correlated with CSF soluble TREM2 and showed regional distribution resembling TREM2 gene expression. Network analysis revealed that microglial activation and tau correlated hierarchically with each other following Braak-like stages. Regression analysis revealed that the longitudinal tau propagation pathways depended on the baseline microglia network rather than the tau network circuits. The co-occurrence of Aβ, tau and microglia abnormalities was the strongest predictor of cognitive impairment in our study population. Our findings support a model where an interaction between Aβ and activated microglia sets the pace for tau spread across Braak stages.

DOI: 10.1038/s41591-021-01456-w

Source: https://www.nature.com/articles/s41591-021-01456-w

期刊信息

Nature Medicine:《自然—医学》,创刊于1995年。隶属于施普林格·自然出版集团,最新IF:30.641
官方网址:https://www.nature.com/nm/
投稿链接:https://mts-nmed.nature.com/cgi-bin/main.plex