IDENTIFICATION OF SEPTINS IN NEUROFIBRILLARY TANGLES IN ALZHEIMERS-DISEASE

Septins are evolutionarily conserved cytoskeletal GTPases that can for m heteropolymer complexes involved hi cytokinesis and other cellular p rocesses. We detected expression of the human septin genes Nedd5, H5, Diff6, and hCDC10 in postmortem brain tissues using the reverse transc ription-coupled polymerase chain reaction and their products by immuno blot analysis, Four antibodies directed against three septins, Nedd5, H5, and Diff6, consistently labeled neurofibrillary tangles, neuropil threads, and dystrophic neurites in the senile plaques in brains affec ted by Alzheimer's disease but did not label obvious structures in you ng control brains. Immunoelectron microscopy revealed that Nedd5 local ized to the paired helical filaments, Pre-tangles, the precursory gran ular deposits that accumulate in the neuronal cytoplasm, also were lab eled with the antibodies. These findings suggest that at least the thr ee septins are associated with tau-based paired helical filament core, and may contribute to the formation of neurofibrillary tangle as inte gral constitutents of paired helical filaments.