Elevated levels of matrix metalloproteinases-9 and -1 and of tissue inhibitors of MMPs, TIMP-1 and TIMP-2 in postmortem brain tissue of progressive supranuclear palsy.

We determined the levels and tissue localization of matrix metalloproteinases (MMPs) as well as their endogenous tissue inhibitors (TIMPs) in postmortem brain tissue from 13 patients with progressive supranuclear palsy (PSP) and 8 age-matched controls. MMP-9 expression was significantly increased in both the frontal cortex (p=0.002) and substantia nigra (p=0.003) of PSP cases as compared to controls whereas MMP-1 levels were increased in the substantia nigra (p=0.01) but unchanged in the frontal cortex (p=0.41). Levels of the endogenous tissue inhibitors of MMPs, TIMP-1 and TIMP-2 were significantly elevated in the substantia nigra (TIMP-1: p=0.004, TIMP-2: p=0.01). Levels of TIMPs were unchanged in PSP frontal cortex as compared to control cases. Together, these data show alterations of MMPs and TIMPs in the substantia nigra as well as in the frontal cortex of PSP, consistent with the possibility that alterations in MMPs/TIMPs may contribute to disease pathogenesis.