Summary
Neurofibrillary tangles in Alzheimer’s disease are composed of abnormal filaments whose biochemical composition is partly resolved. Cytoskeletal proteins are major components of these abnormal fibers, the microtubule-associated protein tau being the main constituent demonstrated in neurofibrillary tangles. Other cytoskeletal proteins or fragments of them which have been immunologically detected in tangles are the microtubule-associated protein MAP2 and neurofilament 150- and 200-kDa polypeptides. We have isolated a cDNA encoding epitope shared between MAP2 and neurofibrillary tangles, as demonstrated by immunocytochemistry with an antiserum raised against a fusion protein. In situ hybridization with this cDNA on tissue sections of the hippocampus in Alzheimer’s disease did not show increases in the hybridization signal in tangle-bearing neurons. These results suggest that the accumulation of MAP2 immunoreactivity in neurofibrillary tangles is not directly related to an overex-pression of this protein. This also strengthens the hypothesis implicating post-translational modifications of cytoskeletal proteins as mechanisms of neurofibrillary tangles formation.
This work was supported by grants from the Belgian FNRS, FRFC, and FRSM (numbers 96048082, 90548082, 90148082), NATO, The Wellcome Trust, and the MRC.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
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
Brion JP, Passareiro H, 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 (Brux) 95:229–235
Brion JP, Cheetham M, Robinson PA, Couck AM, Anderton BH (1987) Isolation of cDNAs coding for epitopes shared by microtubule-associated proteins and neurofibrillary tangles in Alzheimer’s disease. FEBS Lett 226:28–32
Brion JP, Guilleminot J, Couchie D, Flament-Durand J, Nunez J (1988) Both adult and juvenile tau microtubule-associated proteins are axon specific in the developing and adult rat cerebellum. Neuroscience 25:139–146
Brion JP, Power D, Hue D, Couck AM, Anderton BH, Flament-Durand J (1989) Heterogeneity of ubiquitin immunoreactivity in neurofibrillary tangles of Alzheimer’s disease. Neurochem Int 14:121–128
Couchie D, Nunez J (1985) Immunological characterization of microtubule-associated proteins specific for the immature brain. FEBS Lett 188:331–335
Dammerman M, Goldstein M, Yen SHC, Shafit-Zagardo В (1988) Isolation and characterization of cDNA clones encoding epitopes shared with Alzheimer neurofibrillary tangles. J Neurosci Res 19:43–51
Delacourte A, Défossez A (1986) Alzheimer’s disease: tau proteins, the promoting factors of microtubule assembly, are major components of paired helical filaments. J Neurol Sci 76:173–186
Dustin Ρ, Flament-Durand J (1982) Disturbances of axoplasmic transport in Alzheimer’s disease. In: Weiss DG, Gorio A (eds) Axoplasmic transport in physiology and pathology. Springer, Berlin Heidelberg New York, pp 131–136
Duyckaerts C, Brion JP, Hauw J J, Flament-Durand J (1987) Comparison of immuno-cytochemistry with a specific antibody and Bodian’s protargol method. Quantitative assessment of the density of neurofibrillary tangles and senile plaques in senile dementia of the Alzheimer type. Acta Neuropathol (Beri) 73:167–170
Feinberg A, Vogelstein В (1983) A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity. Anal Biochem 132:6–13
Flament-Durand J, Couck AM (1979) Spongiform alterations in brain biopsies of presenile dementia. Acta Neuropathol (Beri) 46:159–162
Garner CG, Matus A (1988) Different forms of microtubule-associated protein 2 are encoded by separate mRNA transcripts. J Cell Biol 106:779–783
Garner CG, Brugg B, Matus A (1988) A 70-kilodalton microtubule-associated protein (MAP2c), related to MAP2. J Neurochem 50:609–615
Goedert M, Wischik CM, Corwther RA, Walter JE, Klug A (1988) Cloning and sequencing of the cDNA encoding a core protein of the paired helical filament of Alzheimer’s disease: identification as the microtubule-associated protein tau. Proc Natl Acad Sci USA 85:4051–4055
Goedert M, Spillantini MG, Potier MC, Ulrich J, Crowther RA (1989) 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 8:393–399
Grundke-Iqbal I, Iqbal K, Quinlan M, Tung YC, Zaidi MS, Wiśniewski HM (1986a) Microtubule- associated protein tau: a component of Alzheimer paired helical filaments. J Biol Chem 261:6084–6089
Grundke-Iqbal I, Iqbal K, Tung YC, Quinlan M, Wiśniewski HM, Binder LI (1986b) Abnormal phosphorylation of the microtubule-associated protein tau in Alzheimer cytoskeletal pathology. Proc Natl Acad Sci USA 83:4913–4917
Huynh TV, Young RA, Davis RW (1985) Constructing and screening cDNA libraries in XgtlO and Xgtll. In: Glover DM (ed) DNA cloning: a practical approach, vol 1. IRL Press, Oxford, pp 49–78
Kang J, Lemaire HG, Unterbeck A, Salbaum JM, Masters CL, Grzeschik KH, Multhaup G, Beyreuther K, Müller-Hill В (1987) The precursor of Alzheimer’s disease amyloid A4 protein resembles a cell-surface receptor. Nature 325:733–736
Kosik KS, Duffy LK, Dowling MM, Abraham C, 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
Kosik KS, Joachim CL, Selkoe DJ (1986) The 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
Kosik KS, Orecchio LD, Bakalis S, Duffy L, Neve RL (1988a) Partial sequence of MAP2 in the region of a shared epitope with Alzheimer neurofibrillary tangles. J Neurochem 51:587–598
Kosik KS, Orecchio LD, Binder L, Trojanowski JQ, Lee VMY, Lee G (1988b) Epitopes that span the tau molecule are shared with paired helical filaments. Neuron 1:817–825
Ksiezak-Reding H, Yen SH (1987) Two monoclonal antibodies recognize Alzheimer’s neurofibrillary tangles, neurofilament, and microtubule-associated proteins. J Neurochem 48:455–462
Lewis SA, Villasante A, Sherline P, Cowan NJ (1986) Brain-specific expression of MAP2 detected using a cloned cDNA probe. J Cell Biol 102:2098–2105
Lewis SA, Wang D, Cowan NJ (1988) Microtubule-associated protein MAP2 shares a microtubule binding motif with tau protein. Science 242:936–939
Masters CL, Multhaup G, Simms G, Pottgiesser J, Martins RN, Beyreuther К (1985) Neuronal origin of a cerebral amyloid: neurofibrillary tangles of Alzheimer’s disease contain the same protein as the amyloid plaque cores and blood vessels. EMBO J 4:2757–2763
Miller CCJ, 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 neurofilaments side arms. EMBO J 5:269–276
Mori H, Kondo J, Ihara Y (1987) Ubiquitin is a component of paired helical filaments in Alzheimer’s disease. Science 325:1641–1644
Neve RL, Selkoe DJ, Kurnitt DM, Kosik KS (1986) A cDNA for a human microtubule associated protein 2 epitope in the Alzheimer neurofibrillary tangle. Mol Brain Res 1:193–196
Nukina N, Ihara Y (1986) One of the antigenic determinants of paired helical filaments is related to tau protein. J Biochem 99:1541–1544
Perry G, Rizzuto N, Autilio-Gambetti L, Gambetti Ρ (1985) Paired helical filaments from Alzheimer disease patients contain cytoskeletal components. Proc Natl Acad Sci USA 82:3916–3920
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
Selkoe DJ, Abraham CR, Podlisny MB, Duffy L (1986) Isolation of low molecular weight proteins from amyloid plaque fibres in Alzheimer’s disease. J Neurochem 45:1820–1834
Sternberger NH, Sternberger LA, Ulrich J (1985) Aberrant neurofilament phosphorylation in Alzheimer disease. Proc Natl Acad Sci USA 82:4274–4276
Wilcock GK, Esiri MM (1982) Plaques, tangles and dementia. A quantitative study. J Neurol Sci 56:343–356
Wischik CM, Novak M, Thogersen 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 disease. Proc Natl Acad Sci USA 85:4506–4510
Wood JG, Mirra SS, Pollock NJ, Binder LI (1986) Neurofibrillary tangles of Alzheimer disease share antigenic determinants with the axonal microtubule-associated protein tau. Proc Natl Acad Sci USA 83:4040–4043
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 protein tau and MAP2. Am J Pathol 126:81–91
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1989 Springer-Verlag Berlin Heidelberg
About this paper
Cite this paper
Brion, J.P., Couck, A.M., Cheetham, M.E., Hanger, D., Anderton, B.H., Flament-Durand, J. (1989). A cDNA Encodes Epitopes Shared Between Microtubule-Associated Protein MAP2 and Alzheimer Neurofibrillary Tangles: In Situ Hybridization and Immunocytochemistry. In: Boller, F., Katzman, R., Rascol, A., Signoret, JL., Christen, Y. (eds) Biological Markers of Alzheimer’s Disease. Research and Perspectives in Alzheimer’s Disease. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-46690-8_6
Download citation
DOI: https://doi.org/10.1007/978-3-642-46690-8_6
Publisher Name: Springer, Berlin, Heidelberg
Print ISBN: 978-3-642-46692-2
Online ISBN: 978-3-642-46690-8
eBook Packages: Springer Book Archive