Christina Toomey, PhD, UCL Queen Square Institute of Neurology, London, UK, discusses a study of the impact of triggering receptor expressed on myeloid cells 2 (TREM2) variant expression on the pathological burden and protein expression changes in postmortem brains with and without Alzheimer’s disease (AD). The results showed that TREM2+ control brains had no beta amyloid (Aβ) or tau deposition and no differences in Aβ or tau were seen in the sporadic AD brains with or without a TREM2 variant. Differences were seen in microglial load, canonical pathways, and biological functions, with upregulation of several pathways in TREM2+ and TREM2- sporadic AD and familial AD, but downregulation in TREM2+ controls. The observation of microglial and expression changes but no AD pathology in TREM2+ controls suggests that other unknown factors may be implicated in AD onset, with TREM2 influencing the microglial involvement in disease pathogenesis. This interview took place during the AD/PD™ 2021 conference.