Immunohistochemical localization of tissue factor pathway inhibitor-1 (TFPI-1), a Kunitz proteinase inhibitor, in Alzheimer's disease.
Senile plaques in Alzheimer's disease (AD) are composed principally of A beta, a 4 kDa fragment of the amyloid precursor protein (APP). Longer forms of APP which contain a Kunitz proteinase inhibitor (KPI) domain are elevated in aged and in AD brains. Tissue factor pathway inhibitor-1 (TFPI) contains three tandem KPI domains and has been well characterized for its role as a natural anticoagulant in the extrinsic coagulation pathway. Functionally, the first two KPI domains of TFPI bind and inhibit the activity of factor Xa and VIIa respectively. In addition, TFPI and APP-KPI share a common clearance mechanism through the low density lipoprotein receptor-related protein (LRP). As part of an ongoing study of the role of KPI-containing proteins in AD, the current study examines TFPI localization in the brain. We report here that TFPI is immunohistochemically localized to microglia in both AD and non-AD individuals and is localized to some senile plaques in AD. Western blot analyses indicate that the amount of TFPI is elevated in frontal cortex samples from AD brains. We propose that TFPI may play a cell specific role in proteinase regulation in the brain.
Hollister
R D
RD
Neurology Service, Massachusetts General Hospital, Boston, USA.
Kisiel
W
W
Hyman
B T
BT
D000544:Alzheimer Disease / Q000378:metabolism*; D001923:Brain Chemistry / Q000502:physiology*; D016022:Case-Control Studies; D005625:Frontal Lobe / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008074:Lipoproteins / Q000032:analysis*; D008970:Molecular Weight; D009419:Nerve Tissue Proteins / Q000032:analysis*; D015842:Serine Proteinase Inhibitors / Q000032:analysis*
D008074:Lipoproteins; D009419:Nerve Tissue Proteins; D015842:Serine Proteinase Inhibitors; C051928:lipoprotein-associated coagulation inhibitor