Fig. 3Figure 3
Schematic representation of complement pathway activation in Alzheimer’s disease (AD). The three complement activation routes, classical (C1q binding to Aβ, tau, or antibody complexes), lectin (Mannose-Binding Lectin [MBL] and its associated MBL-associated serine proteases [MASPs]), and alternative (amplification loop), converge at C3 activation, generating C3a/C5a inflammatory mediators and forming the membrane attack complex (MAC). Excessive activation induces aberrant C1q/C3b-mediated synaptic pruning, microglial and astrocytic activation, and neuronal lysis. Age-related BBB breakdown permits peripheral complement infiltration, while failure of regulatory checkpoints leads to persistent complement-driven neuroinflammation and neurodegeneration in AD