Semi-quantitative rating of complement recognition molecule C1q and products of complement activation C4d (classical and lectin/mannose binding pathways to activation), Bb (alternative pathway) and C3b (all pathways; Figure 2A) revealed increased complement immunoreactivity in progressive MS cases in comparison to non-neurological disease controls and to inflammatory disease controls (which were selected based on the presence of an anatomically matched tissue block that in most cases, did not harbour sites of extensive inflammatory pathology; Figures 2B–E and Supplementary Table 1). Here, C3 is linked to nervous system disorder.