Soyon Hong, PhD, University College London, London, UK, discusses how microglia know which synapses to phagocytose, and what happens when this goes wrong. Microglia, at least in the early stages of Alzheimer’s disease (AD) pathogenesis, are tissue-resident macrophages that respond to signals, such as phosphatidylserine, and initiate synapse destruction. However, in mice that carry risk mutations for AD such as TREM2, microglia cannot differentiate between functional and dysfunctional synapses and this can lead to the emergence of AD. This interview took place at the Alzheimer’s Association International Conference (AAIC) 2022 in San Diego, CA.