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PMID: 9811347 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Identification of septins in neurofibrillary tangles in Alzheimer's disease.

The American journal of pathology ·Vol. 153 ·No. 5 ·1998-11-00 ·Pages 1551-60

Kinoshita A, Kinoshita M, Akiyama H, Tomimoto H, Akiguchi I, Kumar S, Noda M, Kimura J

Abstract

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.

MeSH Terms
Adult Aged Aged, 80 and over Alzheimer Disease/genetics,pathology Antibodies/metabolism Brain/pathology Brain Chemistry Cell Cycle Proteins/analysis,genetics Cytoskeletal Proteins/analysis,genetics GTP Phosphohydrolases/analysis,genetics Humans Immunohistochemistry Microscopy, Immunoelectron Middle Aged Molecular Sequence Data Neurofibrillary Tangles/chemistry,ultrastructure Phosphoric Monoester Hydrolases/analysis,genetics Schizosaccharomyces pombe Proteins Septins Transcription Factors tau Proteins/analysis
Chemicals
Antibodies Cell Cycle Proteins Cytoskeletal Proteins Schizosaccharomyces pombe Proteins Transcription Factors cdc10 protein, S pombe tau Proteins Phosphoric Monoester Hydrolases GTP Phosphohydrolases SEPTIN4 protein, human Sept4 protein, mouse Sept7 protein, mouse Septins
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Kinoshita A
Department of Neurology, Kyoto University Graduate School of Medicine, Japan.
Kinoshita M
Akiyama H
Tomimoto H
Akiguchi I
Kumar S
Noda M
Kimura J
References (45)
45 references, click to expand
  1. Increased expression of neurofilament subunit NF-L produces morphological alterations that resemble the pathology of human motor neuron disease.
    Cell. 1993 Apr 9;73(1):23-33 PMID: 8462100
  2. Localization and possible functions of Drosophila septins.
    Mol Biol Cell. 1995 Dec;6(12):1843-59 PMID: 8590810
  3. Correlative memory deficits, Abeta elevation, and amyloid plaques in transgenic mice.
    Science. 1996 Oct 4;274(5284):99-102 PMID: 8810256
  4. Alz-50 and MC-1, a new monoclonal antibody raised to paired helical filaments, recognize conformational epitopes on recombinant tau.
    J Neurosci Res. 1997 Apr 15;48(2):128-32 PMID: 9130141
  5. A sequence of cytoskeleton changes related to the formation of neurofibrillary tangles and neuropil threads.
    Acta Neuropathol. 1994;87(6):554-67 PMID: 7522386
  6. Identification of a set of genes with developmentally down-regulated expression in the mouse brain.
    Biochem Biophys Res Commun. 1992 Jun 30;185(3):1155-61 PMID: 1378265
  7. The Drosophila peanut gene is required for cytokinesis and encodes a protein similar to yeast putative bud neck filament proteins.
    Cell. 1994 May 6;77(3):371-9 PMID: 8181057
  8. Up-regulation of the Nedd2 gene encoding an ICE/Ced-3-like cysteine protease in the gerbil brain after transient global ischemia.
    J Cereb Blood Flow Metab. 1997 May;17(5):507-14 PMID: 9183288
  9. A purified Drosophila septin complex forms filaments and exhibits GTPase activity.
    J Cell Biol. 1996 May;133(3):605-16 PMID: 8636235
  10. Septin scaffolds and cleavage planes in Saccharomyces.
    Cell. 1996 Jan 26;84(2):187-90 PMID: 8565063
  11. Hyperphosphorylation of tau in PHF.
    Neurobiol Aging. 1995 May-Jun;16(3):365-71; discussion 371-80 PMID: 7566346
  12. Septins may form a ubiquitous family of cytoskeletal filaments.
    J Cell Biol. 1996 Sep;134(6):1345-8 PMID: 8830765
  13. Lymphocyte HEV adhesion variants differ in the expression of multiple gene sequences.
    Gene. 1990 Nov 15;95(2):279-84 PMID: 2174398
  14. Prediction of the coding sequences of unidentified human genes. IV. The coding sequences of 40 new genes (KIAA0121-KIAA0160) deduced by analysis of cDNA clones from human cell line KG-1.
    DNA Res. 1995 Aug 31;2(4):167-74, 199-210 PMID: 8590280
  15. Microtubule-associated protein tau (tau) is a major antigenic component of paired helical filaments in Alzheimer disease.
    Proc Natl Acad Sci U S A. 1986 Jun;83(11):4044-8 PMID: 2424016
  16. Alzheimer-related neuronal protein A68: specificity and distribution.
    Ann Neurol. 1987 Oct;22(4):521-6 PMID: 3435070
  17. Isolation of a fragment of tau derived from the core of the paired helical filament of Alzheimer disease.
    Proc Natl Acad Sci U S A. 1988 Jun;85(12):4506-10 PMID: 3132715
  18. Alzheimer neurofibrillary tangles in diseases other than senile and presenile dementia.
    Ann Neurol. 1979 Mar;5(3):288-94 PMID: 156000
  19. Presenile appearance of abundant Alzheimer's neurofibrillary tangles without senile plaques in the brain in myotonic dystrophy.
    Acta Neuropathol. 1991;82(1):1-5 PMID: 1950473
  20. Nedd5, a mammalian septin, is a novel cytoskeletal component interacting with actin-based structures.
    Genes Dev. 1997 Jun 15;11(12):1535-47 PMID: 9203580
  21. Neurofibrillary tangles but not senile plaques parallel duration and severity of Alzheimer's disease.
    Neurology. 1992 Mar;42(3 Pt 1):631-9 PMID: 1549228
  22. Subunit composition, protein interactions, and structures of the mammalian brain sec6/8 complex and septin filaments.
    Neuron. 1998 Jun;20(6):1111-22 PMID: 9655500
  23. Neuritic pathology and dementia in Alzheimer's disease.
    Ann Neurol. 1991 Aug;30(2):156-65 PMID: 1910274
  24. A Collection of cDNA Clones with Specific Expression Patterns in Mouse Brain.
    Eur J Neurosci. 1990;2(8):704-711 PMID: 12106288
  25. Neurofibrillary tangles in Niemann-Pick disease type C.
    Acta Neuropathol. 1995;89(3):227-38 PMID: 7754743
  26. Progressive neuronopathy in transgenic mice expressing the human neurofilament heavy gene: a mouse model of amyotrophic lateral sclerosis.
    Cell. 1993 Apr 9;73(1):35-46 PMID: 8462101
  27. Glycosylation of microtubule-associated protein tau: an abnormal posttranslational modification in Alzheimer's disease.
    Nat Med. 1996 Aug;2(8):871-5 PMID: 8705855
  28. Immune system response in Alzheimer's disease.
    Can J Neurol Sci. 1989 Nov;16(4 Suppl):516-27 PMID: 2804814
  29. Molecular cloning of a novel human cDNA homologous to CDC10 in Saccharomyces cerevisiae.
    Biochem Biophys Res Commun. 1994 Jul 15;202(1):82-7 PMID: 8037772
  30. Alzheimer's disease: a re-examination of the amyloid hypothesis.
    Trends Neurosci. 1998 Jan;21(1):15-9 PMID: 9464679
  31. Seminars in medicine of the Beth Israel Hospital, Boston. beta-Amyloid and the pathogenesis of Alzheimer's disease.
    N Engl J Med. 1991 Dec 26;325(26):1849-57 PMID: 1961223
  32. The septins: roles in cytokinesis and other processes.
    Curr Opin Cell Biol. 1996 Feb;8(1):106-19 PMID: 8791410
  33. Accumulation of abnormally phosphorylated tau precedes the formation of neurofibrillary tangles in Alzheimer's disease.
    Brain Res. 1989 Jan 16;477(1-2):90-9 PMID: 2495152
  34. Microtubule-associated protein tau. A component of Alzheimer paired helical filaments.
    J Biol Chem. 1986 May 5;261(13):6084-9 PMID: 3084478
  35. New clues to Alzheimer's disease: unraveling the roles of amyloid and tau.
    Nat Med. 1996 Aug;2(8):850-2 PMID: 8705846
  36. Cloning and sequencing of the cDNA encoding a core protein of the paired helical filament of Alzheimer disease: identification as the microtubule-associated protein tau.
    Proc Natl Acad Sci U S A. 1988 Jun;85(11):4051-5 PMID: 3131773
  37. Neurofibrillary tangles of Alzheimer disease share antigenic determinants with the axonal microtubule-associated protein tau (tau)
    Proc Natl Acad Sci U S A. 1986 Jun;83(11):4040-3 PMID: 2424015
  38. Paired helical filaments in electron microscopy of Alzheimer's disease.
    Nature. 1963 Jan 12;197:192-3 PMID: 14032480
  39. Somatodendritic localization and hyperphosphorylation of tau protein in transgenic mice expressing the longest human brain tau isoform.
    EMBO J. 1995 Apr 3;14(7):1304-13 PMID: 7729409
  40. Identification of normal and pathological aging in prospectively studied nondemented elderly humans.
    Neurobiol Aging. 1992 Jan-Feb;13(1):179-89 PMID: 1311804
  41. Making the diagnosis of Alzheimer's disease. A primer for practicing pathologists.
    Arch Pathol Lab Med. 1993 Feb;117(2):132-44 PMID: 8427562
  42. The carboxyl third of tau is tightly bound to paired helical filaments.
    Neuron. 1988 Nov;1(9):827-34 PMID: 2483105
  43. Occurrence of neuropil threads in the senile human brain and in Alzheimer's disease: a third location of paired helical filaments outside of neurofibrillary tangles and neuritic plaques.
    Neurosci Lett. 1986 Apr 24;65(3):351-5 PMID: 2423928
  44. Ubiquitin is a component of paired helical filaments in Alzheimer's disease.
    Science. 1987 Mar 27;235(4796):1641-4 PMID: 3029875
  45. Alternative expression of platelet glycoprotein Ib(beta) mRNA from an adjacent 5' gene with an imperfect polyadenylation signal sequence.
    J Clin Invest. 1997 Feb 1;99(3):520-5 PMID: 9022087
Article Info
Journal
The American journal of pathology
Abbr.
Am J Pathol
ISSN
0002-9440
DOI
10.1016/S0002-9440(10)65743-4
Published
1998-11-00
Pages
1551-60
Language
English
Region
United States
NLM ID
0370502
PMCID
PMC1853406
Subset
IM
Databases
GENBANK
D49382
External Links
PubMed source DOI: 10.1016/S0002-9440(10)65743-4 PMC Full Text View journal details
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