作者
Yingyue Zhou, Wilbur M Song, Prabhakar S Andhey, Amanda Swain, Tyler Levy, Kelly R Miller, Pietro L Poliani, Manuela Cominelli, Shikha Grover, Susan Gilfillan, Marina Cella, Tyler K Ulland, Konstantin Zaitsev, Akinori Miyashita, Takeshi Ikeuchi, Makoto Sainouchi, Akiyoshi Kakita, David A Bennett, Julie A Schneider, Michael R Nichols, Sean A Beausoleil, Jason D Ulrich, David M Holtzman, Maxim N Artyomov, Marco Colonna
发表日期
2020/1/1
期刊
Nature medicine
卷号
26
期号
1
页码范围
131-142
出版商
Nature Publishing Group US
简介
Glia have been implicated in Alzheimer’s disease (AD) pathogenesis. Variants of the microglia receptor triggering receptor expressed on myeloid cells 2 (TREM2) increase AD risk, and activation of disease-associated microglia (DAM) is dependent on TREM2 in mouse models of AD. We surveyed gene-expression changes associated with AD pathology and TREM2 in 5XFAD mice and in human AD by single-nucleus RNA sequencing. We confirmed the presence of Trem2-dependent DAM and identified a previously undiscovered Serpina3n+C4b+ reactive oligodendrocyte population in mice. Interestingly, remarkably different glial phenotypes were evident in human AD. Microglia signature was reminiscent of IRF8-driven reactive microglia in peripheral-nerve injury. Oligodendrocyte signatures suggested impaired axonal myelination and metabolic adaptation to neuronal degeneration. Astrocyte profiles indicated …
学术搜索中的文章
Y Zhou, WM Song, PS Andhey, A Swain, T Levy… - Nature medicine, 2020