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Nat Neurosci. 2019 Jun 24. doi: 10.1038/s41593-019-0433-0. [Epub ahead of print]

TREM2 function impedes tau seeding in neuritic plaques.

Leyns CEG1,2,3, Gratuze M1,2,3, Narasimhan S4, Jain N1,2,3, Koscal LJ1,2,3, Jiang H1,2,3, Manis M1,2,3, Colonna M2,3,5, Lee VMY4, Ulrich JD6,7,8, Holtzman DM9,10,11.

Author information

1
Department of Neurology, Washington University School of Medicine, St. Louis, MO, USA.
2
Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, MO, USA.
3
Knight Alzheimer's Disease Research Center, Washington University School of Medicine, St. Louis, MO, USA.
4
Department of Pathology and Laboratory Medicine, Institute on Aging and Center for Neurodegenerative Disease Research, University of Pennsylvania School of Medicine, Philadelphia, PA, USA.
5
Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA.
6
Department of Neurology, Washington University School of Medicine, St. Louis, MO, USA. ulrichjd@wustl.edu.
7
Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, MO, USA. ulrichjd@wustl.edu.
8
Knight Alzheimer's Disease Research Center, Washington University School of Medicine, St. Louis, MO, USA. ulrichjd@wustl.edu.
9
Department of Neurology, Washington University School of Medicine, St. Louis, MO, USA. holtzman@wustl.edu.
10
Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, MO, USA. holtzman@wustl.edu.
11
Knight Alzheimer's Disease Research Center, Washington University School of Medicine, St. Louis, MO, USA. holtzman@wustl.edu.

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 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.

PMID:
31235932
DOI:
10.1038/s41593-019-0433-0

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