Postmortem changes in the phosphorylation state of tau-protein in the rat brain

The phosphorylation state of tau-protein is crucial for the regulation of n euronal microtubule organization. Functional conclusions on tau-protein req uire an accurate assessment of phosphorylated sites. Therefore, the in vivo distribution and postmortem preservation of some phospho-epitopes on tau-p rotein were examined in the rat brain under different fixation and preparat ion conditions. Detection of tan-protein with a phosphorylation-independent antiserum revealed both axonal and somatodendritic: localizations, which w ere not influenced by a postmortem interval of 30 min. The phospho-epitopes recognized by 12E8, AT8, and PHF-1 were mainly localized in the somatodend ritic compartment. The binding sites of AT8 and PHF-1 were rapidly dephosph orylated postmortem, whereas the Tau-l epitope was unmasked in the somatode ndritic region. The axonally located phospho-epitope of AT270 and the nucle ar epitope of AT100 were still detectable after a postmortem interval of 30 min. Postmortem dephosphorylation and inhibition of this process by PP1 an d/or PP2A was further demonstrated on Western blot. In conclusion, rapid pr ocessing of tau-protein is essential for the correct assessment of investig ations on phospho-isoforms. (C) 1999 Elsevier Science Inc.