C4B and Alzheimer disease: Remarkably, a recent study could show in aged mice that voluntary wheel running leads to a reduction in C4b expression in the hippocampus (Kohman et al., 2011), demonstrating a clear correlation between C4 levels and cognitive abilities, which is further supported by the finding that C4 inhibition by external application of a vaccinia virus complement control protein has beneficial effects on memory performance in mouse models of AD (Kulkarni et al., 2008, 2011).