IMMUNOHISTOCHEMICAL LOCALIZATION OF TISSUE FACTOR PATHWAY INHIBITOR-1(TFPI-1), A KUNITZ PROTEINASE-INHIBITOR, IN ALZHEIMERS-DISEASE

Senile plaques in Alzheimer's disease (AD) are composed principally of A beta, a 4 kDa fragment of the amyloid precursor protein (APP). Long er forms of APP which contain a Kunitz proteinase inhibitor (KPI) doma in are elevated in aged and in AD brains. Tissue factor pathway inhibi tor-1 (TFPI) contains three tandem KPI domains and has been well chara cterized for its role as a natural anticoagulant in the extrinsic coag ulation pathway. Functionally, the first two KPI domains of TFPI bind and inhibit the activity of factor Xa and VIIa respectively. In additi on, TFPI and APP-KPI share a common clearance mechanism through the lo w density lipoprotein receptor-related protein (LRP). As part of an on going study of the role of KPI-containing proteins in AD, the current study examines TFPI localization in the brain. We report here that TFP I is immunohistochemically localized to microglia in both AD and non-A D individuals and is localized to some senile plaques in AD. Western b lot analyses indicate that the amount of TFPI is elevated in frontal c ortex samples from AD brains. We propose that TFPI may play a cell spe cific role in proteinase regulation in the brain.