PKA phosphorylations on tau: Developmental studies in the mouse

PKA phosphorylations of tau may be an early event in the development of neu rofibrillary pathology in Alzheimer's disease, Serines 214 and 409 of tau a re highly phosphorylated in PHF-tau, but are not phosphorylated to any sign ificant extent in normal adult human brain; both of these sites a re phosph orylated in human fetal tissue. To further study this phenomenon, a develop mental characterization of these phosphorylation sites relative to PKA, cAM P-dependent response binding element (CREB) and phosphorylated CREB was per formed using samples from mouse brain. Immunoblot analysis using antibodies specific for phospho-serine 214 (CP-3) and phospho-serine 409 (PG-5) revea led a marked decrease in phosphorylation occurring at each of these sites b etween postnatal day 11 (P11) and P20. Immunoblots with TG-5, a pan-tau ant ibody, revealed uniform expression of tau during postnatal development, as well as a switch in isoform composition that is evident between P7 and P11. This switch in isoform composition just precedes the change in the extent of phosphorylation at serines 214 and 409, and occurs at a time when PKA ph osphorylation of CREB is increasing. Copyright (C) 2000 S. Karger AG, Basel .