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TREM2 expression in the human brain: a marker of monocyte recruitment?

TREM2 expression in the human brain: a marker of monocyte recruitment?
TREM2 expression in the human brain: a marker of monocyte recruitment?
Mutation in the triggering receptor expressed on myeloid cells (TREM) 2 gene has been identified as a risk factor for several neurodegenerative diseases including Alzheimer’s disease (AD). Experimental studies using animal models of AD have highlighted a number of functions associated with TREM2 and its expression by microglial cells. It has therefore been assumed that this is also the case in humans. However, there is very limited information concerning the cellular expression of TREM2 in the human brain. As part of investigations of microglia using post-mortem resources provided by the Medical Research Council Cognitive Function and Ageing Studies (MRC-CFAS), we immunostained the cerebral cortex of 299 participants for TREM2 using the Sigma antibody HPA010917 and compared with the macrophage/microglial markers Iba1 and CD68. As expected, Iba1 and CD68 labelled microglia and perivascular macrophages. However, in most cases (284/299), the TREM2 antibody labelled monocytes within vascular lumens, but not microglia or perivascular macrophages. In contrast, in 5 out of 6 cases with acute infarcts, TREM2 immunoreaction identified cells within the brain parenchyma interpreted as recruited monocytes. Six cases with old infarcts contained phagocytic foamy macrophages which were CD68-positive but TREM2 negative. Our observations, using the HPA010917 anti-TREM2 antibody, suggest that TREM2 is not expressed by microglia but instead seems to be a marker of recruited monocytes in the human brain. This finding has implications with regards to the role of TREM2 as a risk factor, emphasizing the importance of systemic immune responses in the development and progression of Alzheimer’s disease.
TREM2, human brain, dementia, microglia, monocyte, neuropathology
1-21
Fahrenhold, Marie
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Rakic, Sonja
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Classey, John
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Brayne, Carol
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Ince, Paul G.
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Nicoll, James
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Boche, Delphine
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Fahrenhold, Marie
58ddee6a-20b3-4be8-9b87-69d617e639fd
Rakic, Sonja
a6631393-7e52-4df4-a936-00cd2df5b6d4
Classey, John
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Brayne, Carol
978cfad1-c7f6-4f79-aa1c-4f189eaaf035
Ince, Paul G.
c1b8f33a-238f-46ae-8edc-da2594c53e48
Nicoll, James
88c0685f-000e-4eb7-8f72-f36b4985e8ed
Boche, Delphine
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Fahrenhold, Marie, Rakic, Sonja, Classey, John, Brayne, Carol, Ince, Paul G., Nicoll, James and Boche, Delphine (2017) TREM2 expression in the human brain: a marker of monocyte recruitment? Brain Pathology, 1-21. (doi:10.1111/bpa.12564).

Record type: Article

Abstract

Mutation in the triggering receptor expressed on myeloid cells (TREM) 2 gene has been identified as a risk factor for several neurodegenerative diseases including Alzheimer’s disease (AD). Experimental studies using animal models of AD have highlighted a number of functions associated with TREM2 and its expression by microglial cells. It has therefore been assumed that this is also the case in humans. However, there is very limited information concerning the cellular expression of TREM2 in the human brain. As part of investigations of microglia using post-mortem resources provided by the Medical Research Council Cognitive Function and Ageing Studies (MRC-CFAS), we immunostained the cerebral cortex of 299 participants for TREM2 using the Sigma antibody HPA010917 and compared with the macrophage/microglial markers Iba1 and CD68. As expected, Iba1 and CD68 labelled microglia and perivascular macrophages. However, in most cases (284/299), the TREM2 antibody labelled monocytes within vascular lumens, but not microglia or perivascular macrophages. In contrast, in 5 out of 6 cases with acute infarcts, TREM2 immunoreaction identified cells within the brain parenchyma interpreted as recruited monocytes. Six cases with old infarcts contained phagocytic foamy macrophages which were CD68-positive but TREM2 negative. Our observations, using the HPA010917 anti-TREM2 antibody, suggest that TREM2 is not expressed by microglia but instead seems to be a marker of recruited monocytes in the human brain. This finding has implications with regards to the role of TREM2 as a risk factor, emphasizing the importance of systemic immune responses in the development and progression of Alzheimer’s disease.

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Accepted/In Press date: 2 October 2017
e-pub ahead of print date: 7 October 2017
Keywords: TREM2, human brain, dementia, microglia, monocyte, neuropathology

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Local EPrints ID: 414750
URI: https://eprints.soton.ac.uk/id/eprint/414750
PURE UUID: c09a9517-16d4-461f-88c3-7463c994e19e
ORCID for James Nicoll: ORCID iD orcid.org/0000-0002-9444-7246
ORCID for Delphine Boche: ORCID iD orcid.org/0000-0002-5884-130X

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Date deposited: 10 Oct 2017 16:31
Last modified: 03 Dec 2019 01:54

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Contributors

Author: Marie Fahrenhold
Author: Sonja Rakic
Author: John Classey
Author: Carol Brayne
Author: Paul G. Ince
Author: James Nicoll ORCID iD
Author: Delphine Boche ORCID iD

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