Monoclonal Antibody to Embryonic CNS Antigen A2B5 Provides Evidence for the Involvement of Membrane Components at Sites of Alzheimer Degeneration and Detects Sulfatides as Well as Gangliosides
Ronald E. Majocha
Department of Psychiatry, Harvard Medical School, Boston;
Mailman Research Center McLean Hospital, Belmont;
Neurobiology Laboratory, Department of Psychiatry, Massachusetts General Hospital, Boston;
Search for more papers by this authorFiroze B. Jungalwala
Department of Neurology, Harvard Medical School, Boston, and Eunice K. Shriver Center, Waltham, Massachusetts, U.S.A.
Search for more papers by this authorAnne Rodenrys
Department of Psychiatry, Harvard Medical School, Boston;
Search for more papers by this authorCorresponding Author
Charles A. Marotta
Neuroscience Program, Harvard Medical School, Boston;
Department of Psychiatry, Harvard Medical School, Boston;
Mailman Research Center McLean Hospital, Belmont;
Neurobiology Laboratory, Department of Psychiatry, Massachusetts General Hospital, Boston;
Address correspondence and reprint requests to Dr. C. A. Marotta at Neurobiology Laboratory, Bulfinch 4, Massachusetts General Hospital, Boston, MA 02114, U.S.A.Search for more papers by this authorRonald E. Majocha
Department of Psychiatry, Harvard Medical School, Boston;
Mailman Research Center McLean Hospital, Belmont;
Neurobiology Laboratory, Department of Psychiatry, Massachusetts General Hospital, Boston;
Search for more papers by this authorFiroze B. Jungalwala
Department of Neurology, Harvard Medical School, Boston, and Eunice K. Shriver Center, Waltham, Massachusetts, U.S.A.
Search for more papers by this authorAnne Rodenrys
Department of Psychiatry, Harvard Medical School, Boston;
Search for more papers by this authorCorresponding Author
Charles A. Marotta
Neuroscience Program, Harvard Medical School, Boston;
Department of Psychiatry, Harvard Medical School, Boston;
Mailman Research Center McLean Hospital, Belmont;
Neurobiology Laboratory, Department of Psychiatry, Massachusetts General Hospital, Boston;
Address correspondence and reprint requests to Dr. C. A. Marotta at Neurobiology Laboratory, Bulfinch 4, Massachusetts General Hospital, Boston, MA 02114, U.S.A.Search for more papers by this authorAbstract
Immunohistological and biochemical studies were initiated to determine whether or not neural membrane components were associated with degenerative changes characteristic of Alzheimer's disease (AD). Monoclonal antibody A2B5, developed against embryonic chick retinal cells and previously shown to react with neural surface gangliosides, was applied to formalin-fixed sections of control and AD brain tissue. Frontal cortex and hippocampus of AD cases exhibited high levels of A2B5 immunoreactivity within those neurons undergoing neurofibrillary degeneration. Neuritic processes associated with senile plaques were also highly reactive with the A2B5 antibody. The amount of gangliosides and their pattern after HPTLC were the same in control and AD cases. However, the unexpected observation was made that the A2B5 antibody reacted with human brain sulfatides in addition to the expected reactivity with minor gangliosides. The average level of sulfatides in AD brain was significantly higher than in normal controls. The data support the involvement of one or more membrane components with neu-rodegeneration in the Alzheimer brain.
Abbreviations used:
-
- AD
-
- Alzheimer's disease
-
- CHAT
-
- choline ace-tyltransferase
-
- HPTLC
-
- high-performance thin layer chromatography
-
- mab
-
- monoclonal antibody
-
- MAP
-
- microtubule-associated protein
-
- NFT
-
- neurofibrillary tangles
-
- PBS
-
- phosphate-buffered saline
-
- PHF
-
- paired helical filaments
-
- TBS
-
- Tris-buffered saline
REFERENCES
- Agnati L. F., Fuxe K., Calza L., Benfenati F., Cavicchioli L., Toffano F., and Goldstein M. (1983) Gangliosides increase the survival of lesioned nigral dopamine neurons and favor the recovery of dopaminergic synaptic function in striatum of rats by collateral sprouting. Acta. Physiol. Scand. 119, 347–363.
- Arimatsu Y., Naegele J. R., and Barnstable C. J. (1987) Molecular markers of neuronal subpopulations in layers 4, 5 and 6 of cat primary visual cortex. J. Neurosci. 7, 1250–1263.
- Barnstable C. J. (1980) Monoclonal antibodies which recognize different cell types in the rat retina. Nature 286, 231–235.
-
Brion J. P.,
van den Bosch de Aguilar P., and
Flament-Durand J. (1985) in
Advances in Applied Neurological Science, Vol. II Senile Dementia of the Alzheimer Type ( W. H. Gispen and
J. Traber, eds), pp.
164–174. Springer-Verlag,
Berlin
.
10.1007/978-3-642-70644-8_13 Google Scholar
- Brown B. A., Majocha R. E., Staton D. M., and Marotta C. A. (1983) Axonal polypeptides crossreactive with antibodies to neurofilament proteins. J. Neurochem. 40, 299–308.
- Ceccarelli B., Aporti F., and Finesso M. (1976) Effects of brain gangliosides on functional recovery in experimental regeneration and rein nervation. Adv. Exp. Med. Biol. 71, 275–293.
- Chou K. H., Nolan C. E., and Jungalwala F. B. (1982) Composition and metabolism of gangliosides in rat peripheral nervous system during development. J. Neurochem. 39, 1547–1558.
- Chou K. H., Nolan C. E., and Jungalwala F. B. (1985a) Subcellular fractionation of rat sciatic nerve and specific localization of gan-glioside LM1 in rat nerve myelin. J. Neurochem. 44, 1898–1912.
- Chou K. H., Ilyas A. A., Evans J. E., Quarles R. H., and Jungalwala F. B. (1985b) Structure of a glycolipid reacting with monoclonal IgM in neuropathy and with HNK-1. Biochem. Biophys. Res. Commun. 128, 383–388.
- Chou K. H., Schwarting G. A., Evans J. E., and Jungalwala F. B. (1987) Sulfoglucuronyl neolacto scries of glycolipids in peripheral nerves reacting with HNK-1 antibodv. J. Neurochcm. 49, 865–873.
- Cuello A. C., Stephens P. H., Ragari P. C., Sofroniew M. V., and Pearson R. C. A. (1986) Retrograde changes in the nucleus basalis of the rat caused by cortical damage are prevented by exogenous ganglioside GM1. Brain Res. 376, 373–377.
- Eisenbarth G. S., Walsh F. S. and Nirenberg M. (1979) Monoclonal antibody to a plasma membrane antigen of neurons. Proc. Natl. Acad. Sci. 76, 4913–4917.
- Emory C. R., Ala T. A., and Frey W. H. (1987) Ganglioside monoclonal antibody (A2B5) labels Alzheimer's neurofibrillary tangles. Neurology 37, 768–772.
- Fishman P. H. and Brady R. O. (1976) Biosynthesis and function of gangliosides. Science 194, 906–915.
- Folch J., Lees M. B. and Sloane-Stanley G. H. (1957) A simple method for the isolation and purification of total lipids from animal tissues. J. Biol. Chem. 226, 497–509.
- Fredman P., Magnani J. L., Nirenberg M., and Ginsburg V. (1984) Monoclonal antibody A2B5 reacts with many gangliosides in neuronal tissue. Arch. Biochem. Biophys. 233, 661–666.
- Frey W. H., II, Emory C. R., Madsen A. M., Rustan T. D. and Ala T. A. (1987) Alzheimer's neurofibrillary tangles are labeled by ganglioside monoclonal antibody A2B5, in Alzheimer's Disease: Advances in Basic Research and Therapies ( R. J. Wurtman, S. FL. Corkin, and J. H. Growdon, eds), pp. 411–415. Center for Brain Sciences and Metabolism Charitable Trust. Cambridge , Massachusetts .
- Gorio A., Giorgio C., Facci L., and Finesso M. (1980) Motor nerve sprouting induced be ganglioside treatment. Possible implications for gangliosides on neuronal growth. Brain Res. 197, 236–241.
- Grundke-Iqbal I., Iqbal K., Quinlan M., Tung T.-C, Zaidi M. S., and Wisniewski H. M. (1986a) Microtubule-associated protein tau. A component of Alzheimer paired helical filaments. J. Biol. Chem. 261, 6084–6089.
- Grundke-Iqbal I., Iqbal K., Tung Y.-C, Quinlan M., Wisniewski H. M, and Binder L. I. (1986b) Abnormal phosphorylation of the microtubule-associated protein tau in Alzheimer cytoskeletal pathology. Proc. Nail. Acad. Sci. USA 83, 4913–4917.
-
Grundke-Iqbal I.,
Merz P. A.,
Shaikh S. S.,
Wisniewski H. M.,
Ala-fuzoff I., and
Winblad B. (1986c) Defective brain microtubule assembly in Alzheimer's disease.
Lancet
ii, 421–426.
10.1016/S0140-6736(86)92134-3 Google Scholar
- Irwin L. N. (1987) Gangliosides, in Encyclopedia of Neurosciencc, Vol. I ( G. Adelman eds), pp. 446–447. Birkhauser, Boston .
- Kasai N. and Yu R. K. (1983) The monoclonal antibody A2B5 is specific to ganglioside GQlc. Brain Res. 277, 155–158.
- Kean E. L. (1968) Rapid sensitive spectrophotometric method for quantitative determination of sulfatides. J. Lipid Res. 9, 319–327.
- Kundu S. K., Pleatman M. A., Redwine W. A., Boyd A. E., and Marcus D. M. (1983) Binding of monoclonal antibody A2B5 to gangliosides. Biochem Biophys. Res Commun. 116, 835–842.
- Lcdeen R. W. (1984) Biology of gangliosides: neuritogenic and neu-ronotrophic properties. J. Neurosci. Res. 12, 147–159.
- Majocha R. E., Marotta C. A., and Benes F. M. (1985) Immuno-staining of neurofilament protein in human postmortem cortex: a sensitive and specific approach to the pattern analysis of human cortical cytoarchitecture. Can./. Biochem. Cell Biol. 63, 577–584.
- Majocha R. E., Jungalwala F. B., Fulwiler C. E. and Marotta C. A. (1988a) Detection of neurofibrillary tangles and neuritic plaques with neuron-specific monoclonal antibody A2B5, American Association of Neuropathologists (Sixty-Fourth Annual Meeting) Abstr. 99, p. 22.
- Majocha R. E., Benes F. M., Reifel J. L., Rodenrys A. M. and Marotta C. A. (1988b) Laminar-specific distribution and infrastruclural detail of amyloid in the Alzheimer disease cortex visualized by computer-enhanced imaging of epitopes recognized by monoclonal antibodies. Proc. Natl. Acad. Sci. USA 85, 6182–6186.
- Marotta C. A. and Majocha R. E. (1987) A2B5 antibody to a neural surface component localizes to sites of Alzheimer degeneration associated with both neurofibrillary tangles and neuritic plaques. Soc: Neurosci. Abstr. 13, 1151.
- Masters C., Simms G., Weinman N. A., Multhaup G., McDonald B. L. and Beyreuther K. (1985) Amyloid plaque core protein in Alzheimer disease and Down svndrome. Proc. Natl. Acad. Sci. USA 82, 4245–4249.
- Nukina N. and 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., and Gambetti P. (1985) Paired helical filaments from Alzheimer disease patients contain cytoskeletal components. Proc. Natl. Acad. Sci. USA 82, 3916–3920.
- Salim M., Zain S. B., Chou W.-G., Sajdel-Sulkowska E. M., Majocha R. E., Rehman S., Benes F. M., and Marotta C. A. (1988) Molecular cloning of amyloid cDNA from Alzheimer brain messenger RNA. Correlative neuroimmunologic and in situ hybridization studies, in Familial Alzheimer's Disease. Molecular Genetics, Clinical Prospects and Societal Issues ( J. P. Blass, G. D. Miner, L. A. Miner, R. W. Richter, and J. L. Valentine, eds). Marcel Dekker, New York (in press).
- Shelanski M. L., Gaskin F., and Cantor C. (1973) Microtubule assembly in the absence of added nucleotides. Proc. Natl. Acad. Sci. USA 70, 765–768.
- Sofroniew M. V., Pearson R. C. A., Cuello A. C., Tagari P. C., and Stephens P. H. (1986) Parenterally administered GM1 ganglioside presents retrograde degeneration of cholinergic cells of the rat basal forebrain. Brain Res. 398, 393–396.
- Toffano G., Savoini G., Moroni F., Lombardi G., Calza L., and Agnati L. F. (1983) GM1 ganglioside stimulates the regeneration of dopaminergic neurons in the central nervous system. Brain Res. 261, 163–166.
- Tomlinson B. E. and Corsellis J. A. N. (1984) Ageing and dementias, in Greenfield's Neuropathology, 4th edit. ( J. H. Adams, J. A. N. Corsellis, and L. W. Duchen, eds), pp. 951–1025. John Wiley & Sons, New York .
- Wischik C. M., Crowther R. A., Stewart M., and Roth M. (1985) Subunit structure of paired helical filaments in Alzheimer's Disease. J. Cell Biol. 100, 1905–1912.
- Wisniewski H. M. and Terry R. D. (1973) Reexamination of the pathogenesis of the senile plaque, in Progress in Neuropathology ( H. M. Zimmerman, eds), pp. 1–26. Grune & Stratton, New York .
- Wisniewski H. M., Merz G. S., Merz P. A., Wen G. Y., and Iqbal K. (1983) Neurofibrillary tangles and paired helical filaments in Alzheimer's disease, in Neurofilaments ( C. A. Marotta, eds), pp. 196–221. University of Minnesota Press, Minneapolis .
- Wojcik M., Ulas J., and Oderfeld-Nowak B. (1982) The stimulating effect of ganglioside injections on the recovery of choline ace-tyltransferase and acetylcholinesterase activities in the hippocampus of the rat after septal lesions. Neuroscience 7, 495–499.
- Wood J. G., Mirra S. S., Pollock M. FL., and Binder L. I. (1986) Neurofibrillary tangles of Alzheimer disease share antigenic determinants with the axonal microtubule-associated protein tau. Proc. Natl. Acad. Sci. USA 83, 4040.