TREM2 function impedes tau seeding in neuritic plaques

Cheryl E.G. Leyns; Maud Gratuze; Sneha Narasimhan; Nimansha Jain; Lauren J. Koscal; Hong Jiang; Melissa Manis; Marco Colonna; Virginia M.Y. Lee; Jason D. Ulrich; David M. Holtzman

doi:10.1038/s41593-019-0433-0

TREM2 function impedes tau seeding in neuritic plaques

Cheryl E.G. Leyns
, Maud Gratuze
, Sneha Narasimhan
, Nimansha Jain
, Lauren J. Koscal
, Hong Jiang
, Melissa Manis
, Marco Colonna
, Virginia M.Y. Lee
, Jason D. Ulrich
, David M. Holtzman

Research output: Contribution to journal › Article › peer-review

254 Scopus citations

Abstract

Variants in the triggering receptor expressed on myeloid cells 2 (TREM2) have been associated with increased risk for sporadic, late-onset Alzheimer’s disease. Here we show that germline knockout of Trem2 or the TREM2^R47H 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.

Original language	English
Pages (from-to)	1217-1222
Number of pages	6
Journal	Nature neuroscience
Volume	22
Issue number	8
DOIs	https://doi.org/10.1038/s41593-019-0433-0
State	Published - Aug 1 2019

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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 = "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",

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T1 - TREM2 function impedes tau seeding in neuritic plaques

AU - Leyns, Cheryl E.G.

AU - Gratuze, Maud

AU - Narasimhan, Sneha

AU - Jain, Nimansha

AU - Koscal, Lauren J.

AU - Jiang, Hong

AU - Manis, Melissa

AU - Colonna, Marco

AU - Lee, Virginia M.Y.

AU - Ulrich, Jason D.

AU - Holtzman, David M.

PY - 2019/8/1

Y1 - 2019/8/1

N2 - Variants in the triggering receptor expressed on myeloid cells 2 (TREM2) have been associated with increased risk for sporadic, late-onset Alzheimer’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.

AB - Variants in the triggering receptor expressed on myeloid cells 2 (TREM2) have been associated with increased risk for sporadic, late-onset Alzheimer’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.

UR - https://www.scopus.com/pages/publications/85068047136

U2 - 10.1038/s41593-019-0433-0

DO - 10.1038/s41593-019-0433-0

M3 - Article

C2 - 31235932

AN - SCOPUS:85068047136

SN - 1097-6256

VL - 22

SP - 1217

EP - 1222

JO - Nature neuroscience

JF - Nature neuroscience

IS - 8

ER -

TREM2 function impedes tau seeding in neuritic plaques

Abstract

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