Phagocytes as plaque catalysts: Human macrophages generate seeding-competent Aβ42 fibrils with cross-seeding activity - PubMed
6 hours ago
- #Alzheimer's disease
- #Microglia
- #Amyloid beta
- Human phagocytes, including macrophages and microglia, actively produce extracellular, seeding-competent Aβ42 fibrils, challenging the view that they only guard against Aβ accumulation in Alzheimer's disease (AD).
- These cell-generated Aβ42 fibrils differ from synthetic ones, showing enhanced seeding and tau cross-seeding activity in biosensor models.
- Aβ42 fibril formation requires active cellular processes and is worsened by the loss of TREM2, a major AD risk gene.
- Transcriptomic profiling reveals an early inflammatory response similar to microglial states in human AD models.
- The findings suggest microglia and macrophages may have a dual role in AD, acting both as responders and inadvertent facilitators of amyloid assembly, with implications for early therapeutic intervention.