CD33-Dependent Switch Hypothesis: CD33 Antagonism Redirects SPP1 Signaling from Destructive to Restorative

h-var-5cc4b6d5db

CD33 overactivation shifts SPP1-mediated microglial response from restorative (disease-associated microglia pathway) to destructive (excessive synapse engulfment and inflammatory cytokine release). CD33 antagonism converts SPP1 signaling toward neuroprotection by blocking the inhibitory ITIM domain signaling that normally suppresses microglial phagocytosis of amyloid plaques while promoting aberra