Title: Retinal Pathogen Burden as a Boundary-First Amplifier of Alzheimer Progression: A boundary-resilience framing for Chlamydia pneumoniae, NLRP3 activation, and APOE4-linked vulnerability

Abstract Recent human tissue evidence identifies intracellular Chlamydia pneumoniae inclusions in the retina with a higher burden in Alzheimer disease (AD) donors than controls, co-occurring with matched brain findings and scaling with APOE4 carrier status, disease stage, and cognitive deficit. Retinal and cortical proteomics indicate bacterial-infection and NLRP3-inflammasome pathway enrichment. This concept note reframes the finding as a boundary-first progression amplifier: persistent pathogen-associated signaling at CNS-adjacent sensory boundaries can elevate chronic innate immune gain and accelerate downstream neurodegenerative load without requiring a single-pathogen causation claim. We propose falsifiable predictions and minimal monitoring-first study designs to separate initiation vs amplification and to quantify whether retinal biomarkers can function as early-access boundary diagnostics for AD risk stratification. Keywords Alzheimer disease; retina; Chlamydia pneumoniae; APOE4; NLRP3; inflammasome; neuroinflammation; blood-retina barrier; boundary-first; biomarkers; progression amplification