Logo of pnasPNASInfo for AuthorsSubscriptionsAboutThis Article
Proc Natl Acad Sci U S A. 1987 May; 84(9): 3033–3036.
PMCID: PMC304795

Ubiquitin is detected in neurofibrillary tangles and senile plaque neurites of Alzheimer disease brains.


Neurofibrillary tangles (NFT) and neurites associated with senile plaques (SP) in Alzheimer disease-affected brain tissues were specifically immunostained with affinity-purified antibody preparations directed against ubiquitin. In addition, a class of neurites seen in brain regions containing NFT and SP were also specifically stained. Cross-reactivity of the ubiquitin antisera for tau protein, neurofilament proteins, and high molecular weight microtubule-associated proteins (MAPs) were ruled out by (i) the inability of the ubiquitin antisera to stain these proteins in immunoblotting experiments and (ii) the inability of tau, neurofilament, and MAP preparations, when preincubated with the ubiquitin antisera, to inhibit the selective neurofibrillar staining observed. Our results are consistent with the suggestion that ubiquitin is covalently associated with the insoluble neurofibrillary material of NFT and SP. We propose that the ubiquitin-mediated degradative pathway may be ineffective in removing these fibrillar structures in Alzheimer disease brain.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (1.6M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Mann DM. The neuropathology of Alzheimer's disease: a review with pathogenetic, aetiological and therapeutic considerations. Mech Ageing Dev. 1985 Sep;31(3):213–255. [PubMed]
  • Glenner GG. Amyloid deposits and amyloidosis: the beta-fibrilloses (second of two parts). N Engl J Med. 1980 Jun 12;302(24):1333–1343. [PubMed]
  • Hirano A, Dembitzer HM, Kurland LT, Zimmerman HM. The fine structure of some intraganglionic alterations. Neurofibrillary tangles, granulovacuolar bodies and "rod-like" structures as seen in Guam amyotrophic lateral sclerosis and parkinsonism-dementia complex. J Neuropathol Exp Neurol. 1968 Apr;27(2):167–182. [PubMed]
  • Selkoe DJ, Ihara Y, Salazar FJ. Alzheimer's disease: insolubility of partially purified paired helical filaments in sodium dodecyl sulfate and urea. Science. 1982 Mar 5;215(4537):1243–1245. [PubMed]
  • Kosik KS, Joachim CL, Selkoe DJ. 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):4044–4048. [PMC free article] [PubMed]
  • Grundke-Iqbal I, Iqbal K, Quinlan M, Tung YC, Zaidi MS, Wisniewski HM. Microtubule-associated protein tau. A component of Alzheimer paired helical filaments. J Biol Chem. 1986 May 5;261(13):6084–6089. [PubMed]
  • Wood JG, Mirra SS, Pollock NJ, Binder LI. 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):4040–4043. [PMC free article] [PubMed]
  • Perry G, Rizzuto N, Autilio-Gambetti L, Gambetti P. Paired helical filaments from Alzheimer disease patients contain cytoskeletal components. Proc Natl Acad Sci U S A. 1985 Jun;82(11):3916–3920. [PMC free article] [PubMed]
  • Miller CC, Brion JP, Calvert R, Chin TK, Eagles PA, Downes MJ, Flament-Durand J, Haugh M, Kahn J, Probst A, et al. Alzheimer's paired helical filaments share epitopes with neurofilament side arms. EMBO J. 1986 Feb;5(2):269–276. [PMC free article] [PubMed]
  • Hershko A, Ciechanover A. Mechanisms of intracellular protein breakdown. Annu Rev Biochem. 1982;51:335–364. [PubMed]
  • Khachaturian ZS. Diagnosis of Alzheimer's disease. Arch Neurol. 1985 Nov;42(11):1097–1105. [PubMed]
  • Meyer EM, West CM, Chau V. Antibodies directed against ubiquitin inhibit high affinity [3H]choline uptake in rat cerebral cortical synaptosomes. J Biol Chem. 1986 Nov 5;261(31):14365–14368. [PubMed]
  • Haas AL, Bright PM. The immunochemical detection and quantitation of intracellular ubiquitin-protein conjugates. J Biol Chem. 1985 Oct 15;260(23):12464–12473. [PubMed]
  • Shaw G, Osborn M, Weber K. Reactivity of a panel of neurofilament antibodies on phosphorylated and dephosphorylated neurofilaments. Eur J Cell Biol. 1986 Oct;42(1):1–9. [PubMed]
  • Ciechanover A, Elias S, Heller H, Ferber S, Hershko A. Characterization of the heat-stable polypeptide of the ATP-dependent proteolytic system from reticulocytes. J Biol Chem. 1980 Aug 25;255(16):7525–7528. [PubMed]
  • Lindwall G, Cole RD. Phosphorylation affects the ability of tau protein to promote microtubule assembly. J Biol Chem. 1984 Apr 25;259(8):5301–5305. [PubMed]
  • Herzog W, Weber K. Fractionation of brain microtubule-associated proteins. Isolation of two different proteins which stimulate tubulin polymerization in vitro. Eur J Biochem. 1978 Dec 1;92(1):1–8. [PubMed]
  • Delacourte A, Filliatreau G, Boutteau F, Biserte G, Schrevel J. Study of the 10-nm-filament fraction isolated during the standard microtubule preparation. Biochem J. 1980 Nov 1;191(2):543–546. [PMC free article] [PubMed]
  • Braak H, Braak E, Grundke-Iqbal I, Iqbal K. 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):351–355. [PubMed]
  • Ihara Y, Abraham C, Selkoe DJ. Antibodies to paired helical filaments in Alzheimer's disease do not recognize normal brain proteins. Nature. 1983 Aug 25;304(5928):727–730. [PubMed]
  • Hershko A. Ubiquitin: roles in protein modification and breakdown. Cell. 1983 Aug;34(1):11–12. [PubMed]
  • Hershko A, Ciechanover A, Heller H, Haas AL, Rose IA. Proposed role of ATP in protein breakdown: conjugation of protein with multiple chains of the polypeptide of ATP-dependent proteolysis. Proc Natl Acad Sci U S A. 1980 Apr;77(4):1783–1786. [PMC free article] [PubMed]
  • Gregori L, Marriott D, West CM, Chau V. Specific recognition of calmodulin from Dictyostelium discoideum by the ATP, ubiquitin-dependent degradative pathway. J Biol Chem. 1985 May 10;260(9):5232–5235. [PubMed]
  • Ciechanover A, Finley D, Varshavsky A. Ubiquitin dependence of selective protein degradation demonstrated in the mammalian cell cycle mutant ts85. Cell. 1984 May;37(1):57–66. [PubMed]
  • Mita S, Yasuda H, Marunouchi T, Ishiko S, Yamada M. A temperature-sensitive mutant of cultured mouse cells defective in chromosome condensation. Exp Cell Res. 1980 Apr;126(2):407–416. [PubMed]
  • Chin DT, Kuehl L, Rechsteiner M. Conjugation of ubiquitin to denatured hemoglobin is proportional to the rate of hemoglobin degradation in HeLa cells. Proc Natl Acad Sci U S A. 1982 Oct;79(19):5857–5861. [PMC free article] [PubMed]
  • Hershko A, Leshinsky E, Ganoth D, Heller H. ATP-dependent degradation of ubiquitin-protein conjugates. Proc Natl Acad Sci U S A. 1984 Mar;81(6):1619–1623. [PMC free article] [PubMed]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences


Save items

Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...


  • MedGen
    Related information in MedGen
  • PubMed
    PubMed citations for these articles
  • Substance
    PubChem chemical substance records that cite the current articles. These references are taken from those provided on submitted PubChem chemical substance records.

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...