Topoisomerase I inhibition yields a CD74(high)/MHC(high) human microglial subtype with enhanced Aβ uptake.

Topoisomerase I inhibitors induce a human microglial subtype with high CD74 and MHC expression that enhances amyloid beta uptake, reducing toxicity.

• Why it matters: Understanding microglial functional states is crucial for developing therapies for neurodegenerative diseases like Alzheimer's, but linking transcriptomic profiles to cellular functions remains challenging.
• What they did: Researchers treated human microglia and related models with topoisomerase I inhibitors, notably Camptothecin and FDA-approved Topotecan, to induce a specific microglial state characterized by increased antigen presentation and phagocytosis.
• The result: This approach revealed a microglial subtype capable of improved amyloid beta clearance and reduced inflammatory responses, offering a reproducible method to study and potentially modulate microglial functions in neurodegeneration.