TREM2 expression in the human brain: a marker of monocyte recruitment?
Ince, Paul G
Brain pathology (Zurich, Switzerland)
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Fahrenhold, M., Rakic, S., Classey, J., Brayne, C., Ince, P. G., Nicoll, J. A., Boche, D., & et al. (2018). TREM2 expression in the human brain: a marker of monocyte recruitment?. Brain pathology (Zurich, Switzerland), 28 (5), 595-602. https://doi.org/10.1111/bpa.12564
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.
MRC-CFAS, Cerebral Cortex, Microglia, Spleen, Monocytes, Macrophages, Humans, Brain Infarction, Dementia, Microfilament Proteins, Calcium-Binding Proteins, DNA-Binding Proteins, Membrane Glycoproteins, Receptors, Immunologic, Antigens, CD, Antigens, Differentiation, Myelomonocytic, Immunohistochemistry, Cohort Studies, Aged, Aged, 80 and over, Female, Male
The study was supported in part by: a Special Project grant and a Programme grant from the MRC and the Department of Health; the UK NIHR Biomedical Research Centre for Ageing and Age—related Disease Award to the Newcastle-upon-Tyne Hospitals Foundation Trust; the Cambridge Brain Bank is supported by the NIHR Cambridge Biomedical Research Centre; The Cambridgeshire and Peterborough NIHR CLAHRC; Nottingham University Hospitals NHS Trust; University of Sheffield and the Sheffield Teaching Hospitals NHS Foundation Trust; The Thomas Willis Oxford Brain Collection, supported by the Oxford Biomedical Research Centre; The Walton Centre NHS Foundation Trust, Liverpool.
External DOI: https://doi.org/10.1111/bpa.12564
This record's URL: https://www.repository.cam.ac.uk/handle/1810/273509
Attribution 4.0 International
Licence URL: http://creativecommons.org/licenses/by/4.0/