14/07/2026
Yesterday, July 13, we welcomed Santiago Solé Domenech (Weill Cornell Medicine, NY, USA) to Achucarro for a seminar on microglial mechanisms involved in amyloid-beta clearance in Alzheimer’s disease. 🧠
In his talk, “Beyond Phagocytosis: Lysosomal Acidification and Digestive Exophagy in Microglial Alzheimer’s Aβ Clearance, From Cell Culture Models to the Living Brain”, he presented research exploring how microglia degrade fibrillar amyloid-beta plaques that are too large to be eliminated by phagocytosis.
This work describes the process of digestive exophagy, in which microglia form tightly sealed lysosomal synapses on amyloid-beta aggregates and secrete lysosomal contents and protons to promote their degradation. The findings suggest that incomplete acidification of these compartments may limit the efficient degradation of fibrillar amyloid-beta.
The research also presents a novel methodology to measure lysosomal pH in macrophages and microglia in the intact mouse brain. Preliminary results indicate that these cells do not fully acidify their lysosomes, providing new opportunities to investigate how lysosomal acidification influences the clearance of pathogenic fibrils.
Thank you to Santiago Sole Domenech for the visit and for sharing these insights with our community. 👏
