In human MCI and AD retinas, we identify a Chlamydia pneumoniae-Aβ42–linked NLRP3 inflammasome axis: NLRP3, ASC, and caspase-1 correlate strongly with retinal Chlamydia pneumoniae load and Aβ42, and associate with CCasp3 apoptosis, NGSDMD pyroptosis, retinal and brain atrophy, higher Braak stage, and worse MMSE. Here, CASP1 is linked to Brain atrophy.