Transglutaminase activity is increased in Alzheimer's disease brain

Transglutaminase is a calcium-activated enzyme that crosslinks substrate 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 component of these t...

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Bibliographic Details
Published in:Brain research 1997-03, Vol.751 (2), p.323-329
Main Authors: Johnson, Gail V.W, Cox, Teresa M, Lockhart, Jason P, Zinnerman, Marcus D, Miller, Michael L, Powers, Richard E
Format: Article
Language:English
Subjects:
Aged
Alzheimer Disease - enzymology
Alzheimer's disease
Cerebellum - enzymology
Female
Humans
Male
Middle Aged
Neurofibrillary tangle
Prefrontal Cortex - enzymology
Reference Values
Tau protein
Transglutaminase
Transglutaminases - metabolism
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Summary:Transglutaminase is a calcium-activated enzyme that crosslinks substrate 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 component 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 and postmortem interval were used in the analyses. Total transglutaminase activity was significantly higher in the Alzheimer's disease prefrontal cortex compared to control. In addition the levels of tissue transglutaminase, as determined by quantitative immunoblotting, were elevated approximately 3-fold in Alzheimer's disease prefrontal cortex compared to control. To our knowledge, this is the first demonstration that transglutaminase is increased in Alzheimer's disease brain. There were 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 in Alzheimer's disease, it can be suggested that transglutaminase could be a contributing factor in neurofibrillary tangle formation.
ISSN:0006-8993
1872-6240
DOI:10.1016/S0006-8993(96)01431-X