Cerebrospinal fluid tissue transglutaminase as a biochemical marker for Alzheimer's disease

Tissue transglutaminase (tTG) is an indicator of acute cell death in vitro. An increase in tTG protein level is found in postmortem Alzheimer's disease (AD) brains as well as in Huntington's disease. No study revealed tTG in vivo so far. We investigated the concentrations of tTG in the cerebrospinal fluid (CSF) obtained from 84 patients using ELISA assays. We compared 33 patients with probable AD to 18 patients with probable vascular dementia (VaD) and 33 control patients without neuropsychological deficit. Diagnosis was supported by CSF parameter and neuroimaging. We found a highly significant difference (P = 0.001) between the concentration of tTG in the AD groups (7.58 pg/ml) and controls (2.99 pg/ml). There was no statistical difference between controls and VaD (2.93 pg/ml). Interestingly, tTG did not show an association with tau protein, Abeta42, apoE4, neuropsychological items, or age. Males showed lower tTG values than females; however, this difference did not reach statistical significance. To our knowledge, this is the first demonstration that tTG is increased in AD in vivo. Our results suggest that tTG may be a powerful biochemical marker of the acute degenerating process in vivo. It may serve as completion of CSF analysis in the diagnosis of dementing disorders and may be a simple way of assessing the efficacy of possible new antiapoptotic drugs.