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PMID: 2169192 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Molecular analysis of neurofibrillary degeneration in Alzheimer's disease. An immunohistochemical study.

The American journal of pathology ·Vol. 137 ·No. 3 ·1990-09-00 ·Pages 711-23

Bondareff W, Wischik CM, Novak M, Amos WB, Klug A, Roth M

Abstract

Antibodies directed against three regions of tau, ubiquitin, and B-amyloid were used in a histologic study of neurofibrillary degeneration in Alzheimer's disease to distinguish two populations of neurofibrillary tangles. Intracellular tangles were immunolabeled exclusively by two antibodies raised against antigens in the fuzzy coat of the paired helical filament (PHF). Extracellular tangles were distinguished by selective immunolabeling with a monoclonal antibody raised against antigens in the PHF core. This was associated with removal of the fuzzy coat and exposure of PHF-core epitopes. In the transition from intracellular to extracellular compartments in vivo, tangles appeared to undergo changes similar to protease digestion in vitro. The transition was associated with the appearance of amyloid immunoreactivity. These findings suggest that tangle degradation occurs in a series of distinct stages, including ubiquitination of some unknown molecule, a change in tau immunoreactivity, and partial proteolysis of tangle-bound tau in extracellular tangles.

MeSH Terms
Aged Aged, 80 and over Alzheimer Disease/immunology,pathology Amyloid/analysis,immunology Antibodies, Monoclonal Female Hippocampus/immunology,ultrastructure Humans Immunoenzyme Techniques Male Microscopy, Electron Microtubule-Associated Proteins/analysis,immunology Middle Aged Neurofibrils/analysis,immunology,ultrastructure Ubiquitins/analysis,immunology tau Proteins
Chemicals
Amyloid Antibodies, Monoclonal Microtubule-Associated Proteins Ubiquitins tau Proteins
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Bondareff W
Department of Psychiatry and Biological Sciences, University of Southern California, Los Angeles 90033.
Wischik C M
Novak M
Amos W B
Klug A
Roth M
References (50)
50 references, click to expand
  1. Amyloid protein precursor messenger RNAs: differential expression in Alzheimer's disease.
    Science. 1988 Aug 26;241(4869):1080-4 PMID: 2457949
  2. Alzheimer neurofibrillary tangles: monoclonal antibodies to inherent antigen(s).
    Acta Neuropathol. 1984;62(4):268-75 PMID: 6730905
  3. Tau protein immunoreactivity in dementia of the Alzheimer type. I. Morphology, evolution, distribution, and pathogenetic implications.
    Lab Invest. 1989 Jan;60(1):123-37 PMID: 2492060
  4. 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
  5. Subunit structure of paired helical filaments in Alzheimer's disease.
    J Cell Biol. 1985 Jun;100(6):1905-12 PMID: 2581978
  6. Senile plaque amyloid, paired helical filaments, and cerebrovascular amyloid in Alzheimer's disease are all deposits of the same protein.
    Lancet. 1985 Feb 2;1(8423):278 PMID: 2857343
  7. Immunochemical properties of ubiquitin conjugates in the paired helical filaments of Alzheimer disease.
    J Neurochem. 1989 May;52(5):1523-8 PMID: 2468737
  8. Paired helical filaments from Alzheimer disease patients contain cytoskeletal components.
    Proc Natl Acad Sci U S A. 1985 Jun;82(11):3916-20 PMID: 3889918
  9. Aberrant neurofilament phosphorylation in Alzheimer disease.
    Proc Natl Acad Sci U S A. 1985 Jun;82(12):4274-6 PMID: 3159022
  10. Neuronal origin of a cerebral amyloid: neurofibrillary tangles of Alzheimer's disease contain the same protein as the amyloid of plaque cores and blood vessels.
    EMBO J. 1985 Nov;4(11):2757-63 PMID: 4065091
  11. Neuritic plaques and cerebrovascular amyloid in Alzheimer disease are antigenically related.
    Proc Natl Acad Sci U S A. 1985 Dec;82(24):8729-32 PMID: 2934737
  12. Image reconstruction of the Alzheimer paired helical filament.
    EMBO J. 1985 Dec 30;4(13B):3661-5 PMID: 2419127
  13. Subunit structure of the Alzheimer tangle.
    Br Med Bull. 1986 Jan;42(1):51-6 PMID: 3513893
  14. Microtubule-associated protein tau. A component of Alzheimer paired helical filaments.
    J Biol Chem. 1986 May 5;261(13):6084-9 PMID: 3084478
  15. Alzheimer's paired helical filaments share epitopes with neurofilament side arms.
    EMBO J. 1986 Feb;5(2):269-76 PMID: 2423324
  16. One of the antigenic determinants of paired helical filaments is related to tau protein.
    J Biochem. 1986 May;99(5):1541-4 PMID: 2423512
  17. 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
  18. 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
  19. 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
  20. Clinical diagnosis of Alzheimer's disease: report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer's Disease.
    Neurology. 1984 Jul;34(7):939-44 PMID: 6610841
  21. Ubiquitin is associated with abnormal cytoplasmic filaments characteristic of neurodegenerative diseases.
    Proc Natl Acad Sci U S A. 1988 Jun;85(12):4501-5 PMID: 2837768
  22. 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
  23. Alz-50 antibody recognizes Alzheimer-related neuronal changes.
    Ann Neurol. 1988 Apr;23(4):371-9 PMID: 3382173
  24. Structural characterization of the core of the paired helical filament of Alzheimer disease.
    Proc Natl Acad Sci U S A. 1988 Jul;85(13):4884-8 PMID: 2455299
  25. Abnormal phosphorylation of the microtubule-associated protein tau (tau) in Alzheimer cytoskeletal pathology.
    Proc Natl Acad Sci U S A. 1986 Jul;83(13):4913-7 PMID: 3088567
  26. Monoclonal antibodies raised against a subsequence of senile plaque core protein react with plaque cores, plaque periphery and cerebrovascular amyloid in Alzheimer's disease.
    Neurosci Lett. 1986 Jul 24;68(2):252-6 PMID: 3748453
  27. Alzheimer's disease: Tau proteins, the promoting factors of microtubule assembly, are major components of paired helical filaments.
    J Neurol Sci. 1986 Dec;76(2-3):173-86 PMID: 3098926
  28. Conservation of brain amyloid proteins in aged mammals and humans with Alzheimer's disease.
    Science. 1987 Feb 20;235(4791):873-7 PMID: 3544219
  29. Alzheimer's neurofibrillary tangles contain unique epitopes and epitopes in common with the heat-stable microtubule associated proteins tau and MAP2.
    Am J Pathol. 1987 Jan;126(1):81-91 PMID: 2433949
  30. Ubiquitin is a component of paired helical filaments in Alzheimer's disease.
    Science. 1987 Mar 27;235(4796):1641-4 PMID: 3029875
  31. Alzheimer's neurofibrillary tangles are penetrated by astroglial processes and appear eosinophilic in their final stages.
    Acta Neuropathol. 1987;72(3):214-7 PMID: 2436433
  32. Ubiquitin is detected in neurofibrillary tangles and senile plaque neurites of Alzheimer disease brains.
    Proc Natl Acad Sci U S A. 1987 May;84(9):3033-6 PMID: 3033674
  33. Localization of amyloid beta protein messenger RNA in brains from patients with Alzheimer's disease.
    Science. 1987 Jul 3;237(4810):77-80 PMID: 3299701
  34. An evaluation of confocal versus conventional imaging of biological structures by fluorescence light microscopy.
    J Cell Biol. 1987 Jul;105(1):41-8 PMID: 3112165
  35. Ubiquitin-protein conjugates in Alzheimer's lesions.
    Neurosci Lett. 1987 Aug 18;79(1-2):207-12 PMID: 2823191
  36. A special type of senile plaque, possibly an initial stage.
    Acta Neuropathol. 1987;74(2):133-41 PMID: 3673504
  37. Isolation of cDNAs coding for epitopes shared by microtubule-associated proteins and neurofibrillary tangle in Alzheimer's disease.
    FEBS Lett. 1987 Dec 21;226(1):28-32 PMID: 2446926
  38. Axonal disruption and aberrant localization of tau protein characterize the neuropil pathology of Alzheimer's disease.
    Ann Neurol. 1987 Nov;22(5):639-43 PMID: 3122646
  39. Neuronal localization of amyloid beta protein precursor mRNA in normal human brain and in Alzheimer's disease.
    EMBO J. 1987 Dec 1;6(12):3627-32 PMID: 3322812
  40. Ubiquitin and microtubule-associated protein tau immunoreactivity each define distinct structures with differing distributions and solubility properties in Alzheimer brain.
    Proc Natl Acad Sci U S A. 1988 Apr;85(8):2854-8 PMID: 2833758
  41. [Alzheimer's disease, amyloidosis, microglia and astrocytes].
    Rev Neurol (Paris). 1988;144(3):155-7 PMID: 3285438
  42. 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
  43. Intraneuronal and extracellular neurofibrillary tangles exhibit mutually exclusive cytoskeletal antigens.
    Ann Neurol. 1988 Feb;23(2):184-9 PMID: 3377439
  44. Cloning and sequencing of the cDNA encoding an isoform of microtubule-associated protein tau containing four tandem repeats: differential expression of tau protein mRNAs in human brain.
    EMBO J. 1989 Feb;8(2):393-9 PMID: 2498079
  45. Cell biology of the Alzheimer tangle.
    Curr Opin Cell Biol. 1989 Feb;1(1):115-22 PMID: 2517018
  46. Congo red as a stain for fluorescence microscopy of amyloid.
    J Histochem Cytochem. 1965 Nov-Dec;13(8):693-4 PMID: 4160077
  47. Monoclonal antibodies show that neurofibrillary tangles and neurofilaments share antigenic determinants.
    Nature. 1982 Jul 1;298(5869):84-6 PMID: 6178036
  48. Senile dementia of Alzheimer type: astroglial reaction to extracellular neurofibrillary tangles in the hippocampus. An immunocytochemical and electron-microscopic study.
    Acta Neuropathol. 1982;57(1):75-9 PMID: 7090745
  49. Neurofibrillary tangles in senile dementia of the Alzheimer type share an antigenic determinant with intermediate filaments of the vimentin class.
    Am J Pathol. 1983 Dec;113(3):373-81 PMID: 6196977
  50. Ubiquitin-mediated protein degradation.
    J Biol Chem. 1988 Oct 25;263(30):15237-40 PMID: 2844803
Article Info
Journal
The American journal of pathology
Abbr.
Am J Pathol
ISSN
0002-9440
Published
1990-09-00
Pages
711-23
Language
English
Region
United States
NLM ID
0370502
PMCID
PMC1877533
Subset
IM
External Links
PubMed source PMC Full Text View journal details
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