Identification of septins in neurofibrillary tangles in Alzheimer's disease.
Septins are evolutionarily conserved cytoskeletal GTPases that can form heteropolymer complexes involved in cytokinesis and other cellular processes. We detected expression of the human septin genes Nedd5, H5, Diff6, and hCDC100 in postmortem brain tissues using the reverse transcription-coupled polymerase chain reaction and their products by immunoblot 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 affected by Alzheimer's disease but did not label obvious structures in young control brains. Immunoelectron microscopy revealed that Nedd5 localized to the paired helical filaments. Pre-tangles, the precursory granular deposits that accumulate in the neuronal cytoplasm, also were labeled with the antibodies. These findings suggest that at least the three septins are associated with tau-based paired helical filament core, and may contribute to the formation of neurofibrillary tangle as integral constituents of paired helical filaments.
Kinoshita
A
A
Department of Neurology, Kyoto University Graduate School of Medicine, Japan.
Kinoshita
M
M
Akiyama
H
H
Tomimoto
H
H
Akiguchi
I
I
Kumar
S
S
Noda
M
M
Kimura
J
J
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000235:genetics / Q000473:pathology*; D000906:Antibodies / Q000378:metabolism; D001921:Brain / Q000473:pathology; D001923:Brain Chemistry; D018797:Cell Cycle Proteins / Q000032:analysis* / Q000235:genetics; D003598:Cytoskeletal Proteins / Q000032:analysis* / Q000235:genetics; D020558:GTP Phosphohydrolases / Q000032:analysis* / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D016253:Microscopy, Immunoelectron; D008875:Middle Aged; D008969:Molecular Sequence Data; D016874:Neurofibrillary Tangles / Q000737:chemistry* / Q000648:ultrastructure; D010744:Phosphoric Monoester Hydrolases / Q000032:analysis* / Q000235:genetics; D029702:Schizosaccharomyces pombe Proteins; D058112:Septins; D014157:Transcription Factors; D016875:tau Proteins / Q000032:analysis
D000906:Antibodies; D018797:Cell Cycle Proteins; D003598:Cytoskeletal Proteins; D029702:Schizosaccharomyces pombe Proteins; D014157:Transcription Factors; C061178:cdc10 protein, S pombe; D016875:tau Proteins; D010744:Phosphoric Monoester Hydrolases; D020558:GTP Phosphohydrolases; C492027:SEPTIN4 protein, human; C115474:Sept4 protein, mouse; C512895:Sept7 protein, mouse; D058112:Septins