Oligodendrocyte precursor cells-microglia crosstalk via BMP4 drives microglial neuroprotective response and mitigates Alzheimer's disease - PubMed
3 hours ago
- #Alzheimer's disease
- #BMP4
- #Microglia
- Oligodendrocyte precursor cells (OPCs) communicate with microglia via BMP4 to drive a neuroprotective response in Alzheimer's disease (AD).
- BMP4 from late-stage OPCs (COPs) shapes microglial neuroprotective programs, reducing amyloid deposition in AD models.
- Genetic ablation of BMP4 in OPCs suppresses microglial immune responses and worsens amyloid pathology in 5xFAD mice.
- Single-cell RNA sequencing shows BMP4 deficiency in COPs downregulates disease-associated microglia (DAM) genes.
- BMP4-dependent Smad1/5/8 signaling directly regulates Trem2 expression in microglia, promoting beneficial barrier formation around Aβ plaques.
- Replenishing BMP4-expressing COPs or administering AAV-Bmp4 via ICV enhances Trem2+ DAM acquisition and mitigates AD progression.
- The study highlights COP-targeted BMP4 enhancement as a potential therapeutic strategy for AD.