Levels of MMP-9 in serum provide an indication of BBB integrity and although complicated by age-related decline45, sudden elevation towards the clinical end point for prion disease (Fig. 5) may indicate a sudden perturbation leading to exchange of prion material between the CNS and circulating blood and fluctuations in the concentration of prion disease-related PrP isoforms in blood. Here, MMP9 is linked to prion disease.