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

185 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.}",

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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.

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SP - 1217

EP - 1222

JO - Nature neuroscience

JF - Nature neuroscience

IS - 8

ER -

TREM2 function impedes tau seeding in neuritic plaques

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