Thrombin is a
serine protease that is generated by proteolytic cleavage of its precursor,
prothrombin. We previously showed that
thrombin proteolyses the
microtubule-associated protein tau and that phosphorylation of tau inhibits this process. To characterize further the role of
thrombin in the brain, we investigated
prothrombin and
thrombin expression in cultured brain cells and in brains of control,
Alzheimer disease (AD) and
parkinsonism-
dementia complex of Guam (PDCG). We show by
reverse transcriptase-polymerase chain reaction that
prothrombin mRNA is expressed in brain tissues,
neuroblastoma cells, and cultured human astrocytes, oligodendrocytes, and microglial cells. We also show by immunohistochemistry that the
proteins prothrombin and
thrombin are present in brain using specific monoclonal and polyclonal
antibodies for both
proteins. All
antibodies stained residual serum in blood vessels, as well as normal pyramidal neurons and their processes, and some astrocytes. Additionally, in AD and PDCG cases, all
antibodies stained extra- and intracellular neurofibrillary tangles (NFTs),
senile plaques, and reactive microglial cells. The ubiquitous expression of
prothrombin and
thrombin in brain cells suggests that
thrombin plays an important physiological role in normal brain. The accumulation of
thrombin and
prothrombin in NFTs supports the hypothesis that
thrombin may be involved in tau proteolysis and that failure to metabolize tau may lead to its aggregation in
neurodegenerative diseases.