Three different human tau isoforms and rat neurofilament light, middle and heavy chain proteins are cellular...

Abnormal aggregates of tau and neurofilaments are pathologies of Alzheimer's disease. Some of these aggregates are insoluble in chaotropic salts and ionic detergents but the mechanisms that lead to this are not clear. One suggestion is that it is due to crosslinking by tissue transglutaminase. Both tau and neurofilaments can be crosslinked by transglutaminase in vitro and one isoform of tau is now known to be a cellular transglutaminase substrate. However there is no evidence to demonstrate that neurofilaments are cellular substrates for transglutaminase and it is not clear whether other isoforms of tau are equally susceptible to transglutaminase crosslinking. Here, we demonstrate that three different tau isoforms and neurofilament light, middle and heavy chain proteins are all cellular substrates for transglutaminase.