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.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
