作者
Bettina van Lengerich, Lihong Zhan, Dan Xia, Darren Chan, David Joy, Joshua I Park, David Tatarakis, Meredith Calvert, Selina Hummel, Steve Lianoglou, Michelle E Pizzo, Rachel Prorok, Elliot Thomsen, Laura M Bartos, Philipp Beumers, Anja Capell, Sonnet S Davis, Lis de Weerd, Jason C Dugas, Joseph Duque, Timothy Earr, Kapil Gadkar, Tina Giese, Audrey Gill, Johannes Gnörich, Connie Ha, Malavika Kannuswamy, Do Jin Kim, Sebastian T Kunte, Lea H Kunze, Diana Lac, Kendra Lechtenberg, Amy Wing-Sze Leung, Chun-Chi Liang, Isabel Lopez, Paul McQuade, Anuja Modi, Vanessa O Torres, Hoang N Nguyen, Ida Pesämaa, Nicholas Propson, Marvin Reich, Yaneth Robles-Colmenares, Kai Schlepckow, Luna Slemann, Hilda Solanoy, Jung H Suh, Robert G Thorne, Chandler Vieira, Karin Wind-Mark, Ken Xiong, Y Joy Yu Zuchero, Dolo Diaz, Mark S Dennis, Fen Huang, Kimberly Scearce-Levie, Ryan J Watts, Christian Haass, Joseph W Lewcock, Gilbert Di Paolo, Matthias Brendel, Pascal E Sanchez, Kathryn M Monroe
发表日期
2023/3
期刊
Nature neuroscience
卷号
26
期号
3
页码范围
416-429
出版商
Nature Publishing Group US
简介
Loss-of-function variants of TREM2 are associated with increased risk of Alzheimer’s disease (AD), suggesting that activation of this innate immune receptor may be a useful therapeutic strategy. Here we describe a high-affinity human TREM2-activating antibody engineered with a monovalent transferrin receptor (TfR) binding site, termed antibody transport vehicle (ATV), to facilitate blood–brain barrier transcytosis. Upon peripheral delivery in mice, ATV:TREM2 showed improved brain biodistribution and enhanced signaling compared to a standard anti-TREM2 antibody. In human induced pluripotent stem cell (iPSC)-derived microglia, ATV:TREM2 induced proliferation and improved mitochondrial metabolism. Single-cell RNA sequencing and morphometry revealed that ATV:TREM2 shifted microglia to metabolically responsive states, which were distinct from those induced by amyloid pathology. In an AD mouse …
学术搜索中的文章
B van Lengerich, L Zhan, D Xia, D Chan, D Joy, JI Park… - Nature neuroscience, 2023