Home LiteratureArticle Details
PMID: 2116006 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

A preparation of Alzheimer paired helical filaments that displays distinct tau proteins by polyacrylamide gel electrophoresis.

Greenberg SG, Davies P

Abstract

Paired helical filaments (PHFs) are prominent components of Alzheimer disease (AD) neurofibrillary tangles (NFTs). Rather than isolating NFTs, we selected for PHF populations that can be extracted from AD brain homogenates. About 50% of PHF immunoreactivity can be obtained in 27,200 x g supernatants following homogenization in buffers containing 0.8 M NaCl. We further enriched for PHFs by taking advantage of their insolubility in the presence of zwitterionic detergents and 2-mercaptoethanol, removal of aggregates by filtration through 0.45-microns filters, and sucrose density centrifugation. PHF-enriched fractions contained two to five proteins of 57-68 kDa that displayed the same antigenic properties as PHFs. Since the 57- to 68-kDa PHF proteins are antigenically related to tau proteins, they are similar to the tau proteins previously observed in NFTs. However, further analysis revealed that PHF-associated tau can be distinguished from normal, soluble tau by PHF antibodies that do not recognize human adult tau and by one- and two-dimensional PAGE.

MeSH Terms
Actin Cytoskeleton/ultrastructure Adult Aged Aged, 80 and over Alzheimer Disease/pathology Cell Fractionation Centrifugation, Density Gradient Cerebral Cortex/pathology,ultrastructure Cytoskeleton/ultrastructure Electrophoresis, Polyacrylamide Gel Humans Microscopy, Electron Microtubule-Associated Proteins/analysis,isolation & purification Middle Aged Nerve Tissue Proteins/analysis Parietal Lobe/ultrastructure Reference Values Temporal Lobe/ultrastructure tau Proteins
Chemicals
Microtubule-Associated Proteins Nerve Tissue Proteins tau Proteins
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Greenberg S G
Department of Pathology, Albert Einstein College of Medicine, Bronx, NY 10461.
Davies P
References (30)
30 references, click to expand
  1. Cleavage of structural proteins during the assembly of the head of bacteriophage T4.
    Nature. 1970 Aug 15;227(5259):680-5 PMID: 5432063
  2. Protein measurement with the Folin phenol reagent.
    J Biol Chem. 1951 Nov;193(1):265-75 PMID: 14907713
  3. Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications.
    Proc Natl Acad Sci U S A. 1979 Sep;76(9):4350-4 PMID: 388439
  4. Monoclonal antibodies show that neurofibrillary tangles and neurofilaments share antigenic determinants.
    Nature. 1982 Jul 1;298(5869):84-6 PMID: 6178036
  5. Antibodies to paired helical filaments in Alzheimer's disease do not recognize normal brain proteins.
    Nature. 1983 Aug 25-31;304(5928):727-30 PMID: 6350889
  6. Alzheimer paired helical filaments: bulk isolation, solubility, and protein composition.
    Acta Neuropathol. 1984;62(3):167-77 PMID: 6538056
  7. Microtubule-associated protein 2: monoclonal antibodies demonstrate the selective incorporation of certain epitopes into Alzheimer neurofibrillary tangles.
    Proc Natl Acad Sci U S A. 1984 Dec;81(24):7941-5 PMID: 6083566
  8. Monoclonal antibodies to Alzheimer neurofibrillary tangles. 1. Identification of polypeptides.
    Am J Pathol. 1985 Aug;120(2):282-91 PMID: 2411142
  9. A neuronal antigen in the brains of Alzheimer patients.
    Science. 1986 May 2;232(4750):648-50 PMID: 3083509
  10. Microtubule-associated protein tau. A component of Alzheimer paired helical filaments.
    J Biol Chem. 1986 May 5;261(13):6084-9 PMID: 3084478
  11. Paired helical filaments associated with Alzheimer disease are readily soluble structures.
    Brain Res. 1986 Apr 30;372(1):80-8 PMID: 2939924
  12. 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
  13. 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
  14. 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
  15. 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
  16. Ubiquitin is a component of paired helical filaments in Alzheimer's disease.
    Science. 1987 Mar 27;235(4796):1641-4 PMID: 3029875
  17. Altered structural proteins in plaques and tangles: what do they tell us about the biology of Alzheimer's disease?
    Neurobiol Aging. 1986 Nov-Dec;7(6):425-32 PMID: 3104810
  18. The solubility controversy of paired helical filaments: a commentary.
    Neurochem Res. 1987 Jan;12(1):93-5 PMID: 3574590
  19. Recognition of tau epitopes by anti-neurofilament antibodies that bind to Alzheimer neurofibrillary tangles.
    Proc Natl Acad Sci U S A. 1987 May;84(10):3410-4 PMID: 2437579
  20. Recognition of Alzheimer paired helical filaments by monoclonal neurofilament antibodies is due to crossreaction with tau protein.
    Proc Natl Acad Sci U S A. 1987 May;84(10):3415-9 PMID: 3106969
  21. Alzheimer-related neuronal protein A68: specificity and distribution.
    Ann Neurol. 1987 Oct;22(4):521-6 PMID: 3435070
  22. Alz 50, a monoclonal antibody to Alzheimer's disease antigen, cross-reacts with tau proteins from bovine and normal human brain.
    J Biol Chem. 1988 Jun 15;263(17):7943-7 PMID: 3131333
  23. Immunochemical and biochemical characterization of tau proteins in normal and Alzheimer's disease brains with Alz 50 and Tau-1.
    J Biol Chem. 1988 Jun 15;263(17):7948-53 PMID: 3131334
  24. The monoclonal antibody, Alz 50, recognizes tau proteins in Alzheimer's disease brain.
    Neurosci Lett. 1988 May 3;87(3):240-6 PMID: 3132653
  25. 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
  26. Microtubule-associated polypeptides tau are altered in Alzheimer paired helical filaments.
    Brain Res. 1988 Aug;464(1):43-52 PMID: 3141008
  27. Alz 50 recognizes abnormal filaments in Alzheimer's disease and progressive supranuclear palsy.
    Ann Neurol. 1988 Sep;24(3):407-13 PMID: 3067653
  28. A different view of A68 and amyloid.
    Neurobiol Aging. 1989 Sep-Oct;10(5):408-9; discussion 412-4 PMID: 2682319
  29. The carboxyl third of tau is tightly bound to paired helical filaments.
    Neuron. 1988 Nov;1(9):827-34 PMID: 2483105
  30. High resolution two-dimensional electrophoresis of proteins.
    J Biol Chem. 1975 May 25;250(10):4007-21 PMID: 236308
Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
Published
1990-08-00
Pages
5827-31
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC54421
Subset
IM
Grants
NIMH NIH HHS · MH38623 · United States
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]