@article{54105240221b494983f27b19d5607db3,
title = "TREM2 function impedes tau seeding in neuritic plaques",
abstract = "Variants in the triggering receptor expressed on myeloid cells 2 (TREM2) have been associated with increased risk for sporadic, late-onset Alzheimer{\textquoteright}s disease. Here we show that germline knockout of Trem2 or the TREM2R47H variant reduces microgliosis around amyloid-β plaques and facilitates the seeding and spreading of neuritic plaque tau aggregates. These findings demonstrate a key role for TREM2 and microglia in limiting the development of peri-plaque tau pathologies.",
author = "Leyns, {Cheryl E.G.} and Maud Gratuze and Sneha Narasimhan and Nimansha Jain and Koscal, {Lauren J.} and Hong Jiang and Melissa Manis and Marco Colonna and Lee, {Virginia M.Y.} and Ulrich, {Jason D.} and Holtzman, {David M.}",
note = "Funding Information: D.M.H., J.D.U., and H.J. are listed as inventors on a provisional patent from Washington University on TREM2 antibodies. D.M.H., H.J., and C.E.G.L. are listed as inventors on a patent licensed by Washington University to C2N Diagnostics on the therapeutic use of anti-tau antibodies. C.E.G.L. is currently an employee at Merck. M.C. receives research funding from Alector, Amgen, and Ono. D.M.H. co-founded and is on the scientific advisory board of C2N Diagnostics. C2N Diagnostics has licensed certain anti-tau antibodies to AbbVie for therapeutic development. D.M.H. is on the scientific advisory board of Proclara and Denali and consults for Genentech, Eli Lilly, and AbbVie. All other authors have no competing interests. Funding Information: This study was supported by the National Institute of Aging AG053976 (C.E.G.L.), AG059082 (M.C.), AG059176 (M.C.), AG026276 (D.M.H.), AG03991 (D.M.H.), AG05681 (D.M.H.), JPB Foundation (D.M.H.), the Donor{\textquoteright}s Cure Foundation (J.D.U.), and the Cure Alzheimer{\textquoteright}s Fund (D.M.H., M.C.). Scanning of immunohistochemistry was performed on the NanoZoomer digital pathology system courtesy of the Hope Center Alafi Neuroimaging Laboratory. Confocal data were generated on a Zeiss LSM 880 Airyscan Confocal Microscope, which was purchased with support from the Office of Research Infrastructure Programs (ORIP), a part of the NIH Office of the Director under grant OD021629, and in part with support from the Washington University Center for Cellular Imaging (WUCCI). The authors specifically thank M. Shih for his help in automating MATLAB scripts for data quantification, K. Campbell for her assistance with figure design in R studio, and L. Changolkar for assistance with the AD-tau preparation. Publisher Copyright: {\textcopyright} 2019, The Author(s), under exclusive licence to Springer Nature America, Inc.",
year = "2019",
month = aug,
day = "1",
doi = "10.1038/s41593-019-0433-0",
language = "English",
volume = "22",
pages = "1217--1222",
journal = "Nature Neuroscience",
issn = "1097-6256",
number = "8",
}