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. 1987 Dec;84(24):9214–9218. doi: 10.1073/pnas.84.24.9214

Antibodies in cerebrospinal fluid of some Alzheimer disease patients recognize cholinergic neurons in the rat central nervous system.

A McRae-Degueurce 1, S Booj 1, K Haglid 1, L Rosengren 1, J E Karlsson 1, I Karlsson 1, A Wallin 1, L Svennerholm 1, C G Gottfries 1, A Dahlstrom 1
PMCID: PMC299723  PMID: 3321070

Abstract

The etiology of Alzheimer disease is unclear. However, immunological aberrations have been suggested to be critical factors in the pathogenesis of this neurodegenerative disease. This study was carried out to investigate if cerebrospinal fluid (CSF) from Alzheimer disease patients contains antibodies that recognize specific neuronal populations in the rat central nervous system. The results indicate that in a subgroup of patients this is indeed the case. The antibodies reported in this study have the following properties: (i) they recognize neuronal populations and components in the medial septum and spinal motor neurons in rats perfused with a mixture that fixes small neurotransmitter molecules; (ii) adsorption of the patient CSF with staphylococcal protein A-Sepharose and using a polyclonal antiserum against human IgG3 indicates that the immunocytochemical reaction in these brain regions is mainly due to the subclass IgG3; and (iii) the CSF immunocytochemical reaction is blocked by preincubation of the sections with a rabbit anti-acetylcholine antiserum. These results provide evidence that antibodies in the CSF of some, but not all, Alzheimer disease patients recognize acetylcholine-like epitopes in cholinergic neurons in the rat central nervous system.

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Selected References

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  1. Butcher L. L., Talbot K., Bilezikjian L. Acetylcholinesterase neurons in dopamine-containing regions of the brain. J Neural Transm. 1975;37(2):127–153. doi: 10.1007/BF01663629. [DOI] [PubMed] [Google Scholar]
  2. Coyle J. T., Price D. L., DeLong M. R. Alzheimer's disease: a disorder of cortical cholinergic innervation. Science. 1983 Mar 11;219(4589):1184–1190. doi: 10.1126/science.6338589. [DOI] [PubMed] [Google Scholar]
  3. Davies P., Maloney A. J. Selective loss of central cholinergic neurons in Alzheimer's disease. Lancet. 1976 Dec 25;2(8000):1403–1403. doi: 10.1016/s0140-6736(76)91936-x. [DOI] [PubMed] [Google Scholar]
  4. Davies P. Neurotransmitter-related enzymes in senile dementia of the Alzheimer type. Brain Res. 1979 Aug 3;171(2):319–327. doi: 10.1016/0006-8993(79)90336-6. [DOI] [PubMed] [Google Scholar]
  5. Fibiger H. C. The organization and some projections of cholinergic neurons of the mammalian forebrain. Brain Res. 1982 Nov;257(3):327–388. doi: 10.1016/0165-0173(82)90011-x. [DOI] [PubMed] [Google Scholar]
  6. Fudenberg H. H., Whitten H. D., Arnaud P., Khansari N., Tsang K. Y., Hames C. G. Immune diagnosis of a subset of Alzheimer's disease with preliminary implications for immunotherapy. Biomed Pharmacother. 1984;38(6):290–297. [PubMed] [Google Scholar]
  7. Geffard M., McRae-Degueurce A., Souan M. L. Immunocytochemical detection of acetylcholine in the rat central nervous system. Science. 1985 Jul 5;229(4708):77–79. doi: 10.1126/science.3892687. [DOI] [PubMed] [Google Scholar]
  8. Hjelm H., Hjelm K., Sjöquist J. Protein A from Staphylococcus aureus. Its isolation by affinity chromatography and its use as an immunosorbent for isolation of immunoglobulins. FEBS Lett. 1972 Nov 15;28(1):73–76. doi: 10.1016/0014-5793(72)80680-x. [DOI] [PubMed] [Google Scholar]
  9. Houser C. R., Crawford G. D., Barber R. P., Salvaterra P. M., Vaughn J. E. Organization and morphological characteristics of cholinergic neurons: an immunocytochemical study with a monoclonal antibody to choline acetyltransferase. Brain Res. 1983 Apr 25;266(1):97–119. doi: 10.1016/0006-8993(83)91312-4. [DOI] [PubMed] [Google Scholar]
  10. Ingram C. R., Phegan K. J., Blumenthal H. T. Significance of an aging-linked neuron binding gamma globulin fraction of human sera. J Gerontol. 1974 Jan;29(1):20–27. doi: 10.1093/geronj/29.1.20. [DOI] [PubMed] [Google Scholar]
  11. Ishii T., Haga S. Immuno-electron microscopic localization of immunoglobulins in amyloid fibrils of senile plaques. Acta Neuropathol. 1976 Nov 15;36(3):243–249. doi: 10.1007/BF00685368. [DOI] [PubMed] [Google Scholar]
  12. KOELLE G. B. The histochemical identification of acetylcholinesterase in cholinergic, adrenergic and sensory neurons. J Pharmacol Exp Ther. 1955 Jun;114(2):167–184. [PubMed] [Google Scholar]
  13. Kimura H., McGeer P. L., Peng F., McGeer E. G. Choline acetyltransferase-containing neurons in rodent brain demonstrated by immunohistochemistry. Science. 1980 May 30;208(4447):1057–1059. doi: 10.1126/science.6990490. [DOI] [PubMed] [Google Scholar]
  14. Langone J. J. Applications of immobilized protein A in immunochemical techniques. J Immunol Methods. 1982 Dec 30;55(3):277–296. doi: 10.1016/0022-1759(82)90088-6. [DOI] [PubMed] [Google Scholar]
  15. Mayer P. P., Chughtai M. A., Cape R. D. An immunological approach to dementia in the elderly. Age Ageing. 1976 Aug;5(3):164–170. doi: 10.1093/ageing/5.3.164. [DOI] [PubMed] [Google Scholar]
  16. McRae-Degueurce A., Geffard M. One perfusion mixture for immunocytochemical detection of noradrenaline, dopamine, serotonin and acetylcholine in the same rat brain. Brain Res. 1986 Jun 18;376(1):217–219. doi: 10.1016/0006-8993(86)90922-4. [DOI] [PubMed] [Google Scholar]
  17. Mesulam M. M., Mufson E. J., Wainer B. H., Levey A. I. Central cholinergic pathways in the rat: an overview based on an alternative nomenclature (Ch1-Ch6). Neuroscience. 1983 Dec;10(4):1185–1201. doi: 10.1016/0306-4522(83)90108-2. [DOI] [PubMed] [Google Scholar]
  18. Perry E. K., Gibson P. H., Blessed G., Perry R. H., Tomlinson B. E. Neurotransmitter enzyme abnormalities in senile dementia. Choline acetyltransferase and glutamic acid decarboxylase activities in necropsy brain tissue. J Neurol Sci. 1977 Nov;34(2):247–265. doi: 10.1016/0022-510x(77)90073-9. [DOI] [PubMed] [Google Scholar]
  19. Singh V. K., Fudenberg H. H. Detection of brain autoantibodies in the serum of patients with Alzheimer's disease but not Down's syndrome. Immunol Lett. 1986 Jun;12(5-6):277–280. doi: 10.1016/0165-2478(86)90030-1. [DOI] [PubMed] [Google Scholar]
  20. Williams A., Papadopoulos N., Chase T. N. Demonstration of CSF gamma-globulin banding in presenile dementia. Neurology. 1980 Aug;30(8):882–884. doi: 10.1212/wnl.30.8.882. [DOI] [PubMed] [Google Scholar]

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