Accumulation and deposition of Aβ are hallmarks of Alzheimer's disease (AD) and impaired Aβ degradation may be one cause of its accumulation. Plasmin is the key protease of the plasminogen system and can cleave Aβ. The plasminogen system may also play a role in vascular dementia (VaD) via its influence on blood flow. Plasmin is activated from plasminogen by tissue plasminogen activator (tPA) and urokinase-type plasminogen activator (uPA). The activators are regulated by inhibitors which include plasminogen activator inhibitor-1 (PAI-1) and neuroserpin, and plasmin is regulated by inhibitors including α2-antiplasmin and α2-macroglobulin. This thesis describes a series of investigations of the plasminogen system in human postmortem AD and control brain tissue, addressing the hypothesis that plasmin activity is reduced in AD and contributes to the disease through reduced Aβ degradation. Techniques that I optimised or developed were used to investigate the distribution of the key components of the system in temporal cortex, and to measure the mRNA levels of the genes encoding these proteins, plasminogen, plasmin, tPA, neuroserpin and α2-antiplasmin proteins and plasmin activity in AD and control brain tissue. The level of neuron-specific enolase was also assessed, as an indicator of neuronal content in all of the brain samples analysed. The components of the plasminogen system were present mainly in neurons; α2- antiplasmin was also associated with Aβ plaques in AD brain tissue. There was no significant alteration in plasminogen or plasmin in AD at the mRNA, protein or activity level. tPA, uPA, PAI-1 and α2-antiplasmin mRNA, however, were significantly increased in AD compared to controls, as were tPA and α2-antiplasmin protein. Neuroserpin mRNA and protein were reduced. The increases in tPA, uPA, PAI-1 and α2-antiplasmin appear to counteract each other so that plasmin activity is not significantly altered in AD; hence, accumulation of Aβ in AD is not a direct result of altered plasmin activity. Alterations in the activators and inhibitors may, however, influence AD pathogenesis independently of Aβ, through their effects on synaptic plasticity, excitotoxic neuronal death, microglial activation, neuronal migration and apoptosis. My preliminary study of the plasminogen system in VaD has revealed novel significant increases in tPA, neuroserpin, α2-antiplasmin and α2-macroglobulin mRNA relative to NSE in VaD compared to controls. The increases in the inhibitors may contribute to VaD by reducing fibrinolysis and impairing blood flow, whilst the increase in tPA may be protective via enhanced fibrinolysis. This work has revealed a need to investigate the plasminogen system further in both AD and VaD, to confirm the changes and to determine their effects in these diseases.