CRIPTO3 and Mental deterioration: In conclusion, we demonstrated, for the first time, that (1) TBI-induced long-term memory deficits in aged animals are dependent on accumulation of early complement cascade components (C1q, C3, and CR3) in the brain; (2) there is a progressive increase in synaptic engulfment activity by microglia; and (3) inhibition of the classical complement cascade, either through deletion of C3 or inhibition of C1q, provides protection against cognitive decline (see Figure 7).