Expression of embryonic tau protein isoforms persist during adult neurogenesis in the hippocampus

Tau is a microtubule-associated protein with a developmentally regulated expression of multiple isoforms. The neonatal isoform is devoid of two amino terminal inserts and contains only three instead of four microtubuie-binding repeats (0N/3R-tau). We investigated the temporal expression pattern of 0N-tau and 3R-tau in the rat hippocampus. After the decline of 0N-tau and 3R-tau immunoreactivity during the postnatal development both isoforms remain highly expressed in a few cells residing beneath the granule cell layer. Coexpression of the polysialylated neuronal cell adhesion molecule, doublecortin, and incorporated bromode-oxyuridine showed that these cells are proliferating progenitor cells. in contrast mature granule cells express the adult tau protein isoform containing one aminoterminal insert domain (1N-tau). Therefore a shift in tau isoform expression takes place during adult neurogenesis, which might be related to migration, differentiation, and integration in the granule cell layer. A model for studying shifts in tau isoform expression in a defined subset of neurons might help to understand the etiology of tauopathies, when isoform composition is crucial for neurodegeneration, as in Pick's disease or FTDP-17. (c) 2006 Wiley-Liss, Inc.