AD-linked R47H- TREM2 mutation induces disease-enhancing microglial states via AKT hyperactivation

Author:

Sayed Faten A.12ORCID,Kodama Lay1234ORCID,Fan Li3ORCID,Carling Gillian K.3ORCID,Udeochu Joe C.3,Le David2ORCID,Li Qingyun5ORCID,Zhou Lu5,Wong Man Ying3,Horowitz Rose3ORCID,Ye Pearly3,Mathys Hansruedi6ORCID,Wang Minghui7ORCID,Niu Xiang8ORCID,Mazutis Linas9ORCID,Jiang Xueqiao6,Wang Xueting3ORCID,Gao Fuying10,Brendel Matthew11ORCID,Telpoukhovskaia Maria2ORCID,Tracy Tara E.2ORCID,Frost Georgia12ORCID,Zhou Yungui2,Li Yaqiao2,Qiu Yue13ORCID,Cheng Zuolin14ORCID,Yu Guoqiang14ORCID,Hardy John15ORCID,Coppola Giovanni10ORCID,Wang Fei16ORCID,DeTure Michael A.17ORCID,Zhang Bin7ORCID,Xie Lei12ORCID,Trajnowski John Q.18ORCID,Lee Virginia M. Y.18ORCID,Gong Shiaoching3,Sinha Subhash C.3ORCID,Dickson Dennis W.17ORCID,Luo Wenjie3,Gan Li23ORCID

Affiliation:

1. Neuroscience Graduate Program, University of California, San Francisco, San Francisco, CA 94158, USA.

2. Gladstone Institute of Neurological Disease, San Francisco, CA 94107, USA.

3. Helen and Robert Appel Alzheimer’s Disease Research Institute, Brain and Mind Research Institute, Weill Cornell Medicine, New York, NY 10021, USA.

4. Medical Scientist Training Program and Neuroscience Graduate Program, University of California, San Francisco, San Francisco, CA 94143, USA.

5. Department of Neuroscience and Department of Genetics, Washington University School of Medicine, St. Louis, MO 63110, USA.

6. The Picower Institute for Learning and Memory, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.

7. Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, NY 10029, USA.

8. Tri-Institutional Computational Biology and Medicine Program, Weill Cornell Medical College, NY 10065, USA.

9. Computational and Systems Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA

10. Departments of Psychiatry and Neurology, Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA

11. Institute for Computational Biomedicine, Department of Physiology and Biophysics, Weill Cornell Medicine, New York, NY 10021, USA.

12. Chemical Biology Program, Weill Graduate School of Medical Sciences of Cornell University, New York, NY 10065, USA.

13. Department of Computer Science, Hunter College, and The Graduate Center, The City University of New York, New York, NY 10065, USA.

14. Bradley Department of Electrical and Computer Engineering, Virginia Polytechnic Institute and State University, Arlington, VA 24061, USA.

15. Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, Queen Square, London WC1E 6BT, UK.

16. Department of Population Health Sciences, Weill Cornell Medical College, New York, NY 10065, USA.

17. Mayo Clinic, Jacksonville, Florida 32224, USA.

18. Center for Neurodegenerative Disease Research, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.

Abstract

R47H- TREM2 mutation enhances AKT signaling in human AD microglia and mediates proinflammatory and synaptic toxicity in a tauopathy mouse model.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

General Medicine

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