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Specific monoclonal antibodies against normal microtubule-associated protein-2 (MAP2) epitopes present in Alzheimer pathological structures do not recognize paired helical filaments

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Summary

We have developed monoclonal antibodies that detect normal microtubule-associated protein-2 (MAP2) epitopes in routinely fixed, paraffin-embedded tissue. The somatodendritic distribution of MAP2 in bovine and human nervous tissue was confirmed with several of these antibodies. Furthermore, some of these antibodies immunohistochemically labeled certain pathological structures in Alzheimer brain, especially neurites in senile plaques. Electron microscopic observations, however, indicate that these MAP2 epitopes are not located in the Alzheimer paired helical filaments themselves, but in amorphous granular structures coexistent with them. While the pathological nature of these structures is undetermined, they may represent artefactual modifications of normal cytoskeletal components.

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References

  1. Allan VJ, Kreis TE (1986) A microtubule-binding protein associated with membranes of the Golgi apparatus. J Cell Biol 103:2229–2239

    Google Scholar 

  2. Anderton BH, Breinburg D, Downes MJ, Green PJ, Tomlinson BE, Ulrich J, Wood JN, Kahn J (1982) Monoclonal antibodies show that neurofibrillary tangles and neurofilaments share antigenic determinants. Nature 298:84–86

    Google Scholar 

  3. Behrouz N, Defossez A, Delacourte A, Hublau P, Mazzuca M (1989) An antiserum to the N-terminal subsequence of the Alzheimer amyloid Beta protein does not react with neurofibrillary tangles. J Gerontol 44:B156-B159

    Google Scholar 

  4. Bernhardt R, Matus A (1984) Light and electron microscopic studies of the distribution of microtubule-associated protein 2 in rat brain: a difference between dendritic and axonal cytoskeletons. J Comp Neurol 226:203–221

    Google Scholar 

  5. Brion JP, Couck AM, Passareiro E, Flament-Durand J (1985) Neurofibrillary tangles of Alzheimer's disease: an immunohis-tochemical study. J Submicrosc Cytol 17:89–96

    Google Scholar 

  6. Brion JP, Passareiro E, Nunez J, Flament-Durand J (1985) Mise en évidence immunologique de la protéine Tau au niveau des lésions de dégénérescence neurofibrillaire de la maladie d'Alzheimer. Arch Biol 95:229–235

    Google Scholar 

  7. Brion JP, Hanger DP, Bruce MT, Couck AM, Flament-Durand J, Anderton BH (1991) Tau in Alzheimer neurofibrillary tangles: N- and C-terminal regions are differentially associated with paired helical filaments and the location of a putative abnormal phosphorylation site. Biochem J 273:127–133

    Google Scholar 

  8. Caceres A, Payne MR, Binder LI, Steward O (1983) Immunocytochemical localization of actin and microtubule-associated protein MAP2 in dendritic spines. Proc Natl Acad Sci USA 80:1738–1742

    Google Scholar 

  9. Dammerman M, Yen SH, Shafit-Zagardo B (1989) Sequence of a human MAP2 region sharing epitopes with Alzheimer neurofibrillary tangles. J Neurosci Res 24:487–495

    Google Scholar 

  10. Drubin D, Kirschner M (1986) Purification of Tau protein from brain. Methods Enzymol 134:156–159

    Google Scholar 

  11. Dustin P, Flament-Durand J, Vandermot G (1979) Aspects ultrastructuraux du vieillissement cérébral. Bull Mem Acad R Med Belg 134:369–383

    Google Scholar 

  12. Flynn G, Joly JC, Purich DL (1987) The 28.000 Mr microtubule-binding domain of microtubule-associated protein 2 also contains a neurofilament binding site. Biochem Biophys Res Commun 148:1453–1459

    Google Scholar 

  13. Gheuens J, Cras P, Perry G, Boons J, Ceuterick C, Lübke U, Mercken M, Tabaton M, Vandermeeren M, Mulvihill P, Siedlak S, Van Heuverswijn H, Martin JJ (1991) Demonstration of a novel neurofilament-associated antigen in the neurofibrillary pathology of Alzheimer and related diseases. Brain Res 558:43–52

    Google Scholar 

  14. Gilbert SP, Sloboda RD (1986) Identification of a MAP2-like ATP-binding protein associated with axoplasmic vesicles that translocate on isolated microtubules. J Cell Biol 103:947–956

    Google Scholar 

  15. Goedert M, Spillantini MG, Jakes R, Rutherford D, Crowther RA (1989) Multiple isoforms of human microtubule-associated protein Tau: sequences and localization in neurofibrillary tangles of Alzheimer's disease. Neuron 3:519–526

    Google Scholar 

  16. Gray EG, Paula-Barbosa M, Roher A (1987) Alzheimer's disease: paired helical filaments and cytomembranes. Neuropathol Appl Neurobiol 13:91–110

    Google Scholar 

  17. Grundke-Iqbal I, Iqbal K, Quinlan M, Tung YC, Zaidi MS, Wisniewski HM (1986) Microtubule-associated protein Tau a component of Alzheimer paired helical filaments. J Biol Chem 261:6084–6089

    Google Scholar 

  18. Grundke-Iqbal I, Iqbal K, George L, Tung YC, Kim KS, Wisniewski HM (1989) Amyloid protein and neurofibrillary tangles coexist in the same neuron in Alzheimer's disease. Proc Natl Acad Sci USA 86:2853–2857

    Google Scholar 

  19. Guiroy DC, Miyazaki M, Multhaup G, Fischer P, Garruto RM, Beyreuther K, Masters CL, Simms G, Gibbs CJ Jr, Gajdusek DC (1987) Amyloid of neurofibrillary tangles of Guamanian parkinsonism-dementia and Alzheimer disease share identical amino acid sequence. Proc Natl Acad Sci USA 84:2073–2077

    Google Scholar 

  20. Hasegawa M, Arai T, Ihara Y (1990) Immunochemical evidence that fragments of phosphorylated MAP5 (MAP1B) are bound to neurofibrillary tangles in Alzheimer's disease. Neuron 4:909–918

    Google Scholar 

  21. Hirokawa N, Bloom GS, Vallee RB (1985) Cytoskeletal architecture and immunocytochemical localization of microtubule-associated proteins in regions of axons associated with rapid axonal transport: the β,β′-iminodipropionitrile-intoxicated axon as a model system. J Cell Biol 101:227–239

    Google Scholar 

  22. Hsu SM, Raine L, Fanger H (1981) Use of avidin-biotin-peroxidase complex (ABC) in immunoperoxidase techniques: a comparison between ABC and unlabeled antibody (PAP) procedures. J Histochem Cytochem 29:577–580

    Google Scholar 

  23. Kondo J, Honda T, Mori H, Hamada Y, Miura R, Ogawara M, Ihara Y (1988) The carboxyl third of Tau is tightly bound to paired helical filaments. Neuron 1:827–834

    Google Scholar 

  24. Kosik KS, Duffy LK, Dowling MM, Abraham CR, McCluskey A, Selkoe DJ (1984) Microtubule-associated protein 2: monoclonal antibodies demonstrate the selective incorporation of certain epitopes into Alzheimer neurofibrillary tangles. Proc Natl Acad Sci USA 81:7941–7945

    Google Scholar 

  25. Kosik KS, Joachim CL, Selkoe DJ (1986) Microtubule-associated protein Tau is a major antigenic component of paired helical filaments in Alzheimer's disease. Proc Natl Acad Sci USA 83:4044–4048

    Google Scholar 

  26. Kosik KS, Orecchio LD, Bakalis S, Duffy L, Neve RL (1988) Partial sequence of MAP2 in the region of a shared epitope with Alzheimer neurofibrillary tangles. J Neurochem 51:587–598

    Google Scholar 

  27. Kosik KS, Orecchio LD, Binder LI, Trojanowski JQ, Lee VMY, Lee G (1988) Epitopes that span the Tau molecule are shared with paired helical filaments. Neuron 1:817–825

    Google Scholar 

  28. Kziesak-Reding H, Dickson DW, Davies P, Yen SH (1987) Recognition of Tau epitopes by anti-neurofilament antibodies that bind to Alzheimer neurofibrillary tangles. Proc Natl Acad Sci USA 84:3410–3414

    Google Scholar 

  29. Laemmli UK (1970) Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 227:680–685

    Google Scholar 

  30. Lewis SA, Wang D, Cowan NJ (1988) Microtubule-associated protein MAP2 shares a microtubule-binding motif with Tau protein. Science 242:936–939

    Google Scholar 

  31. Lewis SA, Ivanov IE, Lee GH, Cowan NJ (1989) Organization of microtubules in dendrites and axons is determined by a short hydrophobic zipper in microtubule-associated proteins MAP2 and Tau. Nature 342:498–505

    Google Scholar 

  32. Linden M, Nelson BD, Leterrier JF (1989) The specific binding of the microtubule-associated protein-2 (MAP2) to the outer membrane of rat mitochondria. Biochem J 261:167–173

    Google Scholar 

  33. Masters CL, Multhaup G, Simms G, Pottgiesser J, Martins RN, Beyreuther K (1985) 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 4:2757–2763

    Google Scholar 

  34. Mercken M, Vandermeeren M, Six J, Lübke U, Boons J, Vandevoorde A, Gheuens J (1991) Affinity purification of human Tau proteins and the construction of a sensitive sandwich ELISA for human Tau detection. J Neurochem (in press)

  35. Miller CJ, Brion JP, Calvert R, Chin TK, Eagles PAM, Downes MJ, Flament-Durand J, Haugh M, Kahn J, Probst A, Ulrich J, Anderton BH (1986) Alzheimer's paired helical filaments share epitopes with neurofilament side arms. EMBO J 5:269–276

    Google Scholar 

  36. Mori H, Kondo J, Ihara Y (1987) Ubiquitin is a component of paired helical filaments in Alzheimer's disease. Science 235:1641–1644

    Google Scholar 

  37. Nukina N, Ihara Y (1983) Immunocytochemical study on senile plaques in Alzheimer's disease II: abnormal dendrites in senile plaques as revealed by anti-microtubule-associated proteins (MAPs) immunostaining. Proc Jpn Acad 59B:288–292

    Google Scholar 

  38. Nukina N, Kosik KS, Selkoe DJ (1987) Recognition of Alzheimer paired helical filaments by monoclonal neurofilament antibodies is due to crossreaction with Tau protein. Proc Natl Acad Sci USA 84:3415–3419

    Google Scholar 

  39. Perry G, Friedman R, Shaw G, Chau V (1987) Ubiquitin is detected in neurofibrillary tangles and senile plaque neurites of Alzheimer disease brains. Proc Natl Acad Sci USA 84:3033–3036

    Google Scholar 

  40. Rosemblatt M, Fellous A, Mazie JC, Delacourte A, Defossez A (1989) Alzheimer's disease: microtubule-associated proteins 2 (MAP 2) are not components of paired helical filaments. FEBS Lett 252:91–94

    Google Scholar 

  41. Sattilaro RF, Dentler WL, LeCluyse EL(1981) Microtubule-associated proteins (MAPs) and the organization of actin filaments in vitro. J Cell Biol 90:467–473

    Google Scholar 

  42. Sattilano RF (1986) Interaction of microtubule-associated protein 2 with actin filaments. Biochemistry 25:2003–2009

    Google Scholar 

  43. Selkoe DJ, Podlisny MB, Gronbeck A, Mammen A, Kosik KS (1990) Molecular relation of amyloid filaments and paired helical filaments in Alzheimer's disease. Adv Neurol 51:171–179

    Google Scholar 

  44. Sims KB, Crandall JE, Kosik KS, Williams RS (1988) Microtubule-associated protein 2 (MAP 2) immunoreactivity in human fetal neocortex. Brain Res 449:192–200

    Google Scholar 

  45. Steiner B, Mandelkow EM, Biernat J, Gustke N, Meyer HE, Schmidt B, Mieskes G, Söling HD, Drechsel D, Kirshner MW, Goedert M, Mandelkow E (1990) Phosphorylation of microtubule-associated protein Tau: identification of the site for Ca2+ calmodulin dependent kinase and relationship with Tau phosphorylation in Alzheimer tangles. EMBO J 9:3539–3544

    Google Scholar 

  46. Sternberger LA, Hardy PH Jr, Cuculis JJ, Meyer HG (1970) The unlabeled antibody enzyme method of immunohistochemistry: preparation and properties of soluble antigen-antibody complex (horseradish peroxidase-antihorseradish peroxidase) and its use in the identification of spirochetes. J Histochem Cytochem 18:315–333

    Google Scholar 

  47. Trojanowski JQ, Schuck T, Schmidt ML, Lee VMY (1989) Distribution of phosphate-independent MAP2 epitopes revealed with monoclonal antibodies in microwave-denatured human nervous system tissues. J Neurosci Methods 29:171–180

    Google Scholar 

  48. Vallee RB (1986) A taxol-dependent procedure for the isolation of microtubules and microtubule-associated proteins (MAPs). J Cell Biol 92:435–442

    Google Scholar 

  49. Wiche G, Briones E, Hirt H, Krepler R, Artlieb U, Denk H (1983) Differential distribution of microtubule-associated proteins MAP1 and MAP2 in neurons of rat brain and association of MAP1 with microtubules of neuroblastoma cells (clone N2A). EMBO J 2:1915–1920

    Google Scholar 

  50. Wischik CM, Novak M, Thögersen HC, Edwards PC, Runswick MJ, Jakes R, Walker JE, Milstein C, Roth M, Klug A (1988) Isolation of a fragment of Tau derived from the core of the paired helical filament of Alzheimer's disease. Proc Natl Acad Sci USA 85:4506–4510

    Google Scholar 

  51. Wood JG, Mirra SS, Pollock NJ, Binder LI (1986) Neurofibrillary tangles of Alzheimer's disease share antigenic determinants with the axonal microtubule-associated protein Tau. Proc Natl Acad Sci USA 83:4040–4043

    Google Scholar 

  52. Yen SH, Dickson DW, Crowe A, Butler M, Shelanski ML (1987) Alzheimer's neurofibrillary tangles contain unique epitopes and epitopes in common with the heat-stable microtubule-associated proteins Tau and MAP2. Am J Pathol 126:81–91

    Google Scholar 

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Author notes

  1. J. Gheuens

    Present address: Janssen Research Foundation, Beerse, Belgium

Authors and Affiliations

  1. Innogenetics, Ghent, Belgium

    J. Six, M. Mercken, M. Vandermeeren & A. Van de Voorde

  2. Laboratory of Neurobiology, Born-Bunge Foundation, University of Antwerp, UIA, Universiteitsplein 1, B-2610, Wilrijk, Belgium

    J. Six, M. Mercken, M. Vandermeeren & J. Gheuens

  3. Laboratori of Neuropathology, Born-Bunge Foundation, University of Antwerp, UIA, Universiteitsplein 1, B-2610, Wilrijk, Belgium

    U. Lübke, C. Ceuterick & J. Boons

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Six, J., Lübke, U., Mercken, M. et al. Specific monoclonal antibodies against normal microtubule-associated protein-2 (MAP2) epitopes present in Alzheimer pathological structures do not recognize paired helical filaments. Acta Neuropathol 83, 179–189 (1992). https://doi.org/10.1007/BF00308477

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