Increased expression of TREM2 in peripheral cells from mild cognitive impairment patients that progress into Alzheimer's disease

Background and purpose Neuroinflammation plays a role in the aetiopathogenesis of Alzheimer's disease (AD). Triggering receptor expressed on myeloid cells 2 (TREM2), a cell surface receptor of the immunoglobulin superfamily, seems to have protective anti‐inflammatory activity in AD. Methods Triggering receptor expressed on myeloid cells 2 expression was analysed in peripheral blood mononuclear cells from healthy subjects (CT) and from patients with either AD or mild cognitive impairment (MCI). MCI patients were re‐evaluated at a 2‐year follow‐up to investigate their progression to AD (MCI‐AD) or lack thereof (MCI‐MCI). Results Triggering receptor expressed on myeloid cells 2 gene expression was higher in AD than CT patients, but was highest in MCI. At recruitment TREM2 levels were higher in MCI‐AD than in MCI‐MCI, and in MCI‐AD were higher initially than at follow‐up. TREM2 displayed a moderate degree of sensitivity and specificity for identifying MCI‐AD in all MCI patients. Our data showed higher TREM2 levels in allele ε4 of apolipoprotein E (ApoE ε4) carriers than non‐carriers in MCI and particularly in MCI‐AD. Conclusions These data seem to confirm the protective role of TREM2 in the pre‐clinical stage of AD. Upregulation of TREM2 in MCI‐AD could be a mechanism to counteract the activation of neuroinflammatory processes. It is possible that TREM2 and ApoE ε4 interact synergistically in the pre‐clinical stage of AD. Therefore, TREM2 may be useful as an early peripheral biomarker for the development of AD.