Santiago Solé-Domènech, PhD, and Rudy Gregory Jacquet, PhD Candidate, Weill Cornell Medicine, New York, NY, discuss their work looking at the involvement of TREM2 in the digestion of amyloid plaques by microglia. Through a series of pH imaging and super-resolution microscopy experiments, the team demonstrated the occurrence of digestive exophagy in microglia – that is, the formation of extracellular, partially sealed compartments into which lysosomal contents are exocytosed to promote the degradation of amyloid beta (Aβ) deposits. With the knowledge that TREM2 plays a role in the uptake and clearance of Aβ, Dr Solé-Domènech and Mr Jacquet studied the impact of TREM2 knockout of the digestive exophagy process. They noted a significant increase in lysosome exocytosis towards Aβ deposits in the TREM2 knockout cells, as well as a significant decrease in actin polymerization. Dr Solé-Domènech explains how he believes these observations are related, as well as his teams planned next steps to assess whether TREM2 deficiency leads to increased fibril release. This interview took place at the AD/PD™ 2023 congress in Gothenburg, Sweden.
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