Our lab just published a study linking Chlamydia pneumoniae—a common respiratory bacterium—to the aggravation of Alzheimer's disease after finding significantly higher levels of it in the retinas and brains of affected patients. https://t.co/QTQavzOsmw
The correlation between C. pneumoniae burden and GSDMD-mediated pyroptosis in the GCL is compelling, but the 61% deficit in microglial engagement (CAM ratio) is the real signal here. If the MoA for AD progression is pathogen-driven, historical Phase 3 failures of anti-chlamydial antibiotics (e.g., doxycycline/rifampin) suggest that simple bacterial eradication is insufficient once the NLRP3 cascade is primed. Does the data imply that we need to prioritize NLRP3-attenuation over antibiotics, or is the intracellular sequestration in astrocytes creating a PK/PD moat that current standard-of-care cannot penetrate during the MCI window?