TRANSGLUTAMINASE ACTIVITY IS INCREASED IN ALZHEIMERS-DISEASE BRAIN

Transglutaminase is a calcium-activated enzyme that crosslinks substra te proteins into insoluble, often filamentous aggregates resistant to proteases. Because the neurofibrillary tangles in Alzheimer's disease have similar characteristics, and because tau protein, the major compo nent of these tangles is an excellent substrate of transglutaminase in vitro, transglutaminase activity and levels were measured in control and Alzheimer's disease brain. Frozen prefrontal cortex and cerebellum samples from Alzheimer's disease and control cases matched for age an d postmortem interval were used in the analyses. Total transglutaminas e activity was significantly higher in the Alzheimer's disease prefron tal cortex compared to control. In addition the levels of tissue trans glutaminase, as determined by quantitative immunoblotting, were elevat ed approximately 3-fold in Alzheimer's disease prefrontal cortex compa red to control. To our knowledge, this is the first demonstration that transglutaminase is increased in Alzheimer's disease brain. There wer e no significant differences in transglutaminase activity or levels in the cerebellum between control and Alzheimer's disease cases. Because the elevation of transglutaminase in the Alzheimer's disease samples occurred in the prefrontal cortex, where neurofibrillary pathology is usually abundant, and not in the cerebellum, which is usually spared i n Alzheimer's disease, it can be suggested that transglutaminase could be a contributing factor in neurofibrillary tangle formation.