Skip to main content
PMC home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1992 Nov 1;89(21):10016–10020. doi: 10.1073/pnas.89.21.10016

Complement activation by beta-amyloid in Alzheimer disease.

J Rogers 1, N R Cooper 1, S Webster 1, J Schultz 1, P L McGeer 1, S D Styren 1, W H Civin 1, L Brachova 1, B Bradt 1, P Ward 1, et al.
PMCID: PMC50268  PMID: 1438191

Abstract

Alzheimer disease (AD) is characterized by excessive deposition of the beta-amyloid peptide (beta-AP) in the central nervous system. Although several lines of evidence suggest that beta-AP is neurotoxic, a mechanism for beta-AP toxicity in AD brain remains unclear. In this paper we provide both direct in vitro evidence that beta-AP can bind and activate the classical complement cytolytic pathway in the absence of antibody and indirect in situ evidence that such actions occur in the AD brain in association with areas of AD pathology.

Full text

PDF
10016

Images in this article

10017Image
on p.10017
10018Image
on p.10018
10018Image
on p.10018
10019Image
on p.10019

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Abraham C. R., Selkoe D. J., Potter H. Immunochemical identification of the serine protease inhibitor alpha 1-antichymotrypsin in the brain amyloid deposits of Alzheimer's disease. Cell. 1988 Feb 26;52(4):487–501. doi: 10.1016/0092-8674(88)90462-x. [DOI] [PubMed] [Google Scholar]
  2. Akiyama H., Kawamata T., Dedhar S., McGeer P. L. Immunohistochemical localization of vitronectin, its receptor and beta-3 integrin in Alzheimer brain tissue. J Neuroimmunol. 1991 Apr;32(1):19–28. doi: 10.1016/0165-5728(91)90067-h. [DOI] [PubMed] [Google Scholar]
  3. Cooper N. R. The classical complement pathway: activation and regulation of the first complement component. Adv Immunol. 1985;37:151–216. doi: 10.1016/s0065-2776(08)60340-5. [DOI] [PubMed] [Google Scholar]
  4. Eikelenboom P., Stam F. C. Immunoglobulins and complement factors in senile plaques. An immunoperoxidase study. Acta Neuropathol. 1982;57(2-3):239–242. doi: 10.1007/BF00685397. [DOI] [PubMed] [Google Scholar]
  5. Gaskin F., Kingsley B. S., Fu S. M. Autoantibodies to neurofibrillary tangles and brain tissue in Alzheimer's disease. Establishment of Epstein-Barr virus-transformed antibody-producing cell lines. J Exp Med. 1987 Jan 1;165(1):245–250. doi: 10.1084/jem.165.1.245. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Gibson G. E., Peterson C. Calcium and the aging nervous system. Neurobiol Aging. 1987 Jul-Aug;8(4):329–343. doi: 10.1016/0197-4580(87)90072-8. [DOI] [PubMed] [Google Scholar]
  7. Glenner G. G., Wong C. W. Alzheimer's disease: initial report of the purification and characterization of a novel cerebrovascular amyloid protein. Biochem Biophys Res Commun. 1984 May 16;120(3):885–890. doi: 10.1016/s0006-291x(84)80190-4. [DOI] [PubMed] [Google Scholar]
  8. Griffin W. S., Stanley L. C., Ling C., White L., MacLeod V., Perrot L. J., White C. L., 3rd, Araoz C. Brain interleukin 1 and S-100 immunoreactivity are elevated in Down syndrome and Alzheimer disease. Proc Natl Acad Sci U S A. 1989 Oct;86(19):7611–7615. doi: 10.1073/pnas.86.19.7611. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Grundke-Iqbal I., Iqbal K., Tung Y. C., Quinlan M., Wisniewski H. M., Binder L. I. Abnormal phosphorylation of the microtubule-associated protein tau (tau) in Alzheimer cytoskeletal pathology. Proc Natl Acad Sci U S A. 1986 Jul;83(13):4913–4917. doi: 10.1073/pnas.83.13.4913. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Kang J., Lemaire H. G., Unterbeck A., Salbaum J. M., Masters C. L., Grzeschik K. H., Multhaup G., Beyreuther K., Müller-Hill B. The precursor of Alzheimer's disease amyloid A4 protein resembles a cell-surface receptor. Nature. 1987 Feb 19;325(6106):733–736. doi: 10.1038/325733a0. [DOI] [PubMed] [Google Scholar]
  11. Katzman R., Terry R., DeTeresa R., Brown T., Davies P., Fuld P., Renbing X., Peck A. Clinical, pathological, and neurochemical changes in dementia: a subgroup with preserved mental status and numerous neocortical plaques. Ann Neurol. 1988 Feb;23(2):138–144. doi: 10.1002/ana.410230206. [DOI] [PubMed] [Google Scholar]
  12. Koh J. Y., Yang L. L., Cotman C. W. Beta-amyloid protein increases the vulnerability of cultured cortical neurons to excitotoxic damage. Brain Res. 1990 Nov 19;533(2):315–320. doi: 10.1016/0006-8993(90)91355-k. [DOI] [PubMed] [Google Scholar]
  13. Kowall N. W., Kosik K. S. Axonal disruption and aberrant localization of tau protein characterize the neuropil pathology of Alzheimer's disease. Ann Neurol. 1987 Nov;22(5):639–643. doi: 10.1002/ana.410220514. [DOI] [PubMed] [Google Scholar]
  14. Mattson M. P., Cheng B., Davis D., Bryant K., Lieberburg I., Rydel R. E. beta-Amyloid peptides destabilize calcium homeostasis and render human cortical neurons vulnerable to excitotoxicity. J Neurosci. 1992 Feb;12(2):376–389. doi: 10.1523/JNEUROSCI.12-02-00376.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. May P. C., Lampert-Etchells M., Johnson S. A., Poirier J., Masters J. N., Finch C. E. Dynamics of gene expression for a hippocampal glycoprotein elevated in Alzheimer's disease and in response to experimental lesions in rat. Neuron. 1990 Dec;5(6):831–839. doi: 10.1016/0896-6273(90)90342-d. [DOI] [PubMed] [Google Scholar]
  16. McGeer P. L., Akiyama H., Itagaki S., McGeer E. G. Activation of the classical complement pathway in brain tissue of Alzheimer patients. Neurosci Lett. 1989 Dec 15;107(1-3):341–346. doi: 10.1016/0304-3940(89)90843-4. [DOI] [PubMed] [Google Scholar]
  17. McGeer P. L., Akiyama H., Itagaki S., McGeer E. G. Immune system response in Alzheimer's disease. Can J Neurol Sci. 1989 Nov;16(4 Suppl):516–527. doi: 10.1017/s0317167100029863. [DOI] [PubMed] [Google Scholar]
  18. McGeer P. L., Walker D. G., Akiyama H., Kawamata T., Guan A. L., Parker C. J., Okada N., McGeer E. G. Detection of the membrane inhibitor of reactive lysis (CD59) in diseased neurons of Alzheimer brain. Brain Res. 1991 Mar 29;544(2):315–319. doi: 10.1016/0006-8993(91)90071-3. [DOI] [PubMed] [Google Scholar]
  19. Mori S., Sternberger N. H., Herman M. M., Sternberger L. A. Leakage and neuronal uptake of serum protein in aged and Alzheimer brains. A postmortem phenomenon with antemortem etiology. Lab Invest. 1991 Mar;64(3):345–351. [PubMed] [Google Scholar]
  20. Nitsch R. M., Blusztajn J. K., Pittas A. G., Slack B. E., Growdon J. H., Wurtman R. J. Evidence for a membrane defect in Alzheimer disease brain. Proc Natl Acad Sci U S A. 1992 Mar 1;89(5):1671–1675. doi: 10.1073/pnas.89.5.1671. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Oltersdorf T., Ward P. J., Henriksson T., Beattie E. C., Neve R., Lieberburg I., Fritz L. C. The Alzheimer amyloid precursor protein. Identification of a stable intermediate in the biosynthetic/degradative pathway. J Biol Chem. 1990 Mar 15;265(8):4492–4497. [PubMed] [Google Scholar]
  22. Rozemuller J. M., Stam F. C., Eikelenboom P. Acute phase proteins are present in amorphous plaques in the cerebral but not in the cerebellar cortex of patients with Alzheimer's disease. Neurosci Lett. 1990 Oct 30;119(1):75–78. doi: 10.1016/0304-3940(90)90759-3. [DOI] [PubMed] [Google Scholar]
  23. Selkoe D. J. The molecular pathology of Alzheimer's disease. Neuron. 1991 Apr;6(4):487–498. doi: 10.1016/0896-6273(91)90052-2. [DOI] [PubMed] [Google Scholar]
  24. Styren S. D., Civin W. H., Rogers J. Molecular, cellular, and pathologic characterization of HLA-DR immunoreactivity in normal elderly and Alzheimer's disease brain. Exp Neurol. 1990 Oct;110(1):93–104. doi: 10.1016/0014-4886(90)90054-v. [DOI] [PubMed] [Google Scholar]
  25. Walker D. G., McGeer P. L. Complement gene expression in human brain: comparison between normal and Alzheimer disease cases. Brain Res Mol Brain Res. 1992 Jun;14(1-2):109–116. doi: 10.1016/0169-328x(92)90017-6. [DOI] [PubMed] [Google Scholar]
  26. Yamaguchi H., Hirai S., Morimatsu M., Shoji M., Nakazato Y. Diffuse type of senile plaques in the cerebellum of Alzheimer-type dementia demonstrated by beta protein immunostain. Acta Neuropathol. 1989;77(3):314–319. doi: 10.1007/BF00687584. [DOI] [PubMed] [Google Scholar]
  27. Yankner B. A., Duffy L. K., Kirschner D. A. Neurotrophic and neurotoxic effects of amyloid beta protein: reversal by tachykinin neuropeptides. Science. 1990 Oct 12;250(4978):279–282. doi: 10.1126/science.2218531. [DOI] [PubMed] [Google Scholar]

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

RESOURCES