Skip to main content
Journal of Neurology, Neurosurgery, and Psychiatry logoLink to Journal of Neurology, Neurosurgery, and Psychiatry
. 1994 Apr;57(4):419–425. doi: 10.1136/jnnp.57.4.419

Beta amyloid protein deposition in the brain after severe head injury: implications for the pathogenesis of Alzheimer's disease.

G W Roberts 1, S M Gentleman 1, A Lynch 1, L Murray 1, M Landon 1, D I Graham 1
PMCID: PMC1072869  PMID: 8163989

Abstract

In a recent preliminary study it was reported that a severe head injury resulted in the deposition of beta amyloid protein (beta AP) in the cortical ribbon of 30% of patients who survived for less than two weeks. Multiple cortical areas have now been examined from 152 patients (age range 8 weeks-81 years) after a severe head injury with a survival time of between four hours and 2.5 years. This series was compared with a group of 44 neurologically normal controls (age range 51 to 80 years). Immunostaining with an antibody to beta AP confirmed the original findings that 30% of cases of head injury have beta AP deposits in one or more cortical areas. Increasing age seemed to accentuate the extent of beta AP deposition and potential correlations with other pathological changes associated with head injury were also investigated. In addition, beta amyloid precursor protein (beta APP) immunoreactivity was increased in the perikarya of neurons in the vicinity of beta AP deposits. The data from this study support proposals that increased expression of beta APP is part of an acute phase response to neuronal injury in the human brain, that extensive overexpression of beta APP can lead to deposition of beta AP and the initiation of an Alzheimer disease-type process within days, and that head injury may be an important aetiological factor in Alzheimer's disease.

Full text

PDF
422

Images in this article

Selected References

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

  1. Abe K., Tanzi R. E., Kogure K. Selective induction of Kunitz-type protease inhibitor domain-containing amyloid precursor protein mRNA after persistent focal ischemia in rat cerebral cortex. Neurosci Lett. 1991 Apr 29;125(2):172–174. doi: 10.1016/0304-3940(91)90020-t. [DOI] [PubMed] [Google Scholar]
  2. Adams J. H., Doyle D., Ford I., Gennarelli T. A., Graham D. I., McLellan D. R. Diffuse axonal injury in head injury: definition, diagnosis and grading. Histopathology. 1989 Jul;15(1):49–59. doi: 10.1111/j.1365-2559.1989.tb03040.x. [DOI] [PubMed] [Google Scholar]
  3. Adams J. H., Doyle D., Graham D. I., Lawrence A. E., McLellan D. R., Gennarelli T. A., Pastuszko M., Sakamoto T. The contusion index: a reappraisal in human and experimental non-missile head injury. Neuropathol Appl Neurobiol. 1985 Jul-Aug;11(4):299–308. doi: 10.1111/j.1365-2990.1985.tb00027.x. [DOI] [PubMed] [Google Scholar]
  4. Allsop D., Haga S., Bruton C., Ishii T., Roberts G. W. Neurofibrillary tangles in some cases of dementia pugilistica share antigens with amyloid beta-protein of Alzheimer's disease. Am J Pathol. 1990 Feb;136(2):255–260. [PMC free article] [PubMed] [Google Scholar]
  5. Amaducci L. A., Fratiglioni L., Rocca W. A., Fieschi C., Livrea P., Pedone D., Bracco L., Lippi A., Gandolfo C., Bino G. Risk factors for clinically diagnosed Alzheimer's disease: a case-control study of an Italian population. Neurology. 1986 Jul;36(7):922–931. doi: 10.1212/wnl.36.7.922. [DOI] [PubMed] [Google Scholar]
  6. Clinton J., Ambler M. W., Roberts G. W. Post-traumatic Alzheimer's disease: preponderance of a single plaque type. Neuropathol Appl Neurobiol. 1991 Feb;17(1):69–74. doi: 10.1111/j.1365-2990.1991.tb00695.x. [DOI] [PubMed] [Google Scholar]
  7. Corsellis J. A., Bruton C. J., Freeman-Browne D. The aftermath of boxing. Psychol Med. 1973 Aug;3(3):270–303. doi: 10.1017/s0033291700049588. [DOI] [PubMed] [Google Scholar]
  8. Dale G. E., Leigh P. N., Luthert P., Anderton B. H., Roberts G. W. Neurofibrillary tangles in dementia pugilistica are ubiquitinated. J Neurol Neurosurg Psychiatry. 1991 Feb;54(2):116–118. doi: 10.1136/jnnp.54.2.116. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Davies L., Wolska B., Hilbich C., Multhaup G., Martins R., Simms G., Beyreuther K., Masters C. L. A4 amyloid protein deposition and the diagnosis of Alzheimer's disease: prevalence in aged brains determined by immunocytochemistry compared with conventional neuropathologic techniques. Neurology. 1988 Nov;38(11):1688–1693. doi: 10.1212/wnl.38.11.1688. [DOI] [PubMed] [Google Scholar]
  10. Dinarello C. A., Wolff S. M. The role of interleukin-1 in disease. N Engl J Med. 1993 Jan 14;328(2):106–113. doi: 10.1056/NEJM199301143280207. [DOI] [PubMed] [Google Scholar]
  11. French L. R., Schuman L. M., Mortimer J. A., Hutton J. T., Boatman R. A., Christians B. A case-control study of dementia of the Alzheimer type. Am J Epidemiol. 1985 Mar;121(3):414–421. doi: 10.1093/oxfordjournals.aje.a114013. [DOI] [PubMed] [Google Scholar]
  12. Gautrin D., Gauthier S. Alzheimer's disease: environmental factors and etiologic hypotheses. Can J Neurol Sci. 1989 Nov;16(4):375–387. doi: 10.1017/s0317167100029425. [DOI] [PubMed] [Google Scholar]
  13. Gentleman S. M., Bruton C., Allsop D., Lewis S. J., Polak J. M., Roberts G. W. A demonstration of the advantages of immunostaining in the quantification of amyloid plaque deposits. Histochemistry. 1989;92(4):355–358. doi: 10.1007/BF00500553. [DOI] [PubMed] [Google Scholar]
  14. Gentleman S. M., Graham D. I., Roberts G. W. Molecular pathology of head trauma: altered beta APP metabolism and the aetiology of Alzheimer's disease. Prog Brain Res. 1993;96:237–246. doi: 10.1016/s0079-6123(08)63270-7. [DOI] [PubMed] [Google Scholar]
  15. Gentleman S. M., Nash M. J., Sweeting C. J., Graham D. I., Roberts G. W. Beta-amyloid precursor protein (beta APP) as a marker for axonal injury after head injury. Neurosci Lett. 1993 Oct 1;160(2):139–144. doi: 10.1016/0304-3940(93)90398-5. [DOI] [PubMed] [Google Scholar]
  16. Gentleman S., Roberts G. Risk factors in Alzheimer's disease. BMJ. 1992 Jan 11;304(6819):118–119. doi: 10.1136/bmj.304.6819.118-d. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Graham D. I., Ford I., Adams J. H., Doyle D., Teasdale G. M., Lawrence A. E., McLellan D. R. Ischaemic brain damage is still common in fatal non-missile head injury. J Neurol Neurosurg Psychiatry. 1989 Mar;52(3):346–350. doi: 10.1136/jnnp.52.3.346. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Hardy J., Allsop D. Amyloid deposition as the central event in the aetiology of Alzheimer's disease. Trends Pharmacol Sci. 1991 Oct;12(10):383–388. doi: 10.1016/0165-6147(91)90609-v. [DOI] [PubMed] [Google Scholar]
  19. Hardy J. Framing beta-amyloid. Nat Genet. 1992 Jul;1(4):233–234. doi: 10.1038/ng0792-233. [DOI] [PubMed] [Google Scholar]
  20. Kawarabayashi T., Shoji M., Harigaya Y., Yamaguchi H., Hirai S. Expression of APP in the early stage of brain damage. Brain Res. 1991 Nov 1;563(1-2):334–338. doi: 10.1016/0006-8993(91)91558-i. [DOI] [PubMed] [Google Scholar]
  21. McGeer P. L., Rogers J. Anti-inflammatory agents as a therapeutic approach to Alzheimer's disease. Neurology. 1992 Feb;42(2):447–449. doi: 10.1212/wnl.42.2.447. [DOI] [PubMed] [Google Scholar]
  22. Nakamura Y., Takeda M., Niigawa H., Hariguchi S., Nishimura T. Amyloid beta-protein precursor deposition in rat hippocampus lesioned by ibotenic acid injection. Neurosci Lett. 1992 Feb 17;136(1):95–98. doi: 10.1016/0304-3940(92)90656-r. [DOI] [PubMed] [Google Scholar]
  23. Ohgami T., Kitamoto T., Tateishi J. Alzheimer's amyloid precursor protein accumulates within axonal swellings in human brain lesions. Neurosci Lett. 1992 Feb 17;136(1):75–78. doi: 10.1016/0304-3940(92)90651-m. [DOI] [PubMed] [Google Scholar]
  24. Roberts G. W., Gentleman S. M., Lynch A., Graham D. I. beta A4 amyloid protein deposition in brain after head trauma. Lancet. 1991 Dec 7;338(8780):1422–1423. doi: 10.1016/0140-6736(91)92724-g. [DOI] [PubMed] [Google Scholar]
  25. Roberts G. W. Immunocytochemistry of neurofibrillary tangles in dementia pugilistica and Alzheimer's disease: evidence for common genesis. Lancet. 1988 Dec 24;2(8626-8627):1456–1458. doi: 10.1016/s0140-6736(88)90934-8. [DOI] [PubMed] [Google Scholar]
  26. Roberts G. W., Nash M., Ince P. G., Royston M. C., Gentleman S. M. On the origin of Alzheimer's disease: a hypothesis. Neuroreport. 1993 Jan;4(1):7–9. doi: 10.1097/00001756-199301000-00001. [DOI] [PubMed] [Google Scholar]
  27. Roberts G. W., Whitwell H. L., Acland P. R., Bruton C. J. Dementia in a punch-drunk wife. Lancet. 1990 Apr 14;335(8694):918–919. doi: 10.1016/0140-6736(90)90520-f. [DOI] [PubMed] [Google Scholar]
  28. Royston M. C., Rothwell N. J., Roberts G. W. Alzheimer's disease: pathology to potential treatments? Trends Pharmacol Sci. 1992 Apr;13(4):131–133. doi: 10.1016/0165-6147(92)90047-a. [DOI] [PubMed] [Google Scholar]
  29. Rudelli R., Strom J. O., Welch P. T., Ambler M. W. Posttraumatic premature Alzheimer's disease. Neuropathologic findings and pathogenetic considerations. Arch Neurol. 1982 Sep;39(9):570–575. doi: 10.1001/archneur.1982.00510210040009. [DOI] [PubMed] [Google Scholar]
  30. Schubert W., Prior R., Weidemann A., Dircksen H., Multhaup G., Masters C. L., Beyreuther K. Localization of Alzheimer beta A4 amyloid precursor protein at central and peripheral synaptic sites. Brain Res. 1991 Nov 1;563(1-2):184–194. doi: 10.1016/0006-8993(91)91532-6. [DOI] [PubMed] [Google Scholar]
  31. Scott J. N., Parhad I. M., Clark A. W. Beta-amyloid precursor protein gene is differentially expressed in axotomized sensory and motor systems. Brain Res Mol Brain Res. 1991 Jul;10(4):315–325. doi: 10.1016/0169-328x(91)90090-k. [DOI] [PubMed] [Google Scholar]
  32. Seubert P., Vigo-Pelfrey C., Esch F., Lee M., Dovey H., Davis D., Sinha S., Schlossmacher M., Whaley J., Swindlehurst C. Isolation and quantification of soluble Alzheimer's beta-peptide from biological fluids. Nature. 1992 Sep 24;359(6393):325–327. doi: 10.1038/359325a0. [DOI] [PubMed] [Google Scholar]
  33. Shedden P. M., Moulton R. J., Sullivan I., Hotz G., Tucker W. S., Muller P. J. Effect of population characteristics on head injury mortality. Pediatr Neurosurg. 1990;16(4-5):203–207. doi: 10.1159/000120527. [DOI] [PubMed] [Google Scholar]
  34. Shoji M., Golde T. E., Ghiso J., Cheung T. T., Estus S., Shaffer L. M., Cai X. D., McKay D. M., Tintner R., Frangione B. Production of the Alzheimer amyloid beta protein by normal proteolytic processing. Science. 1992 Oct 2;258(5079):126–129. doi: 10.1126/science.1439760. [DOI] [PubMed] [Google Scholar]
  35. Siman R., Card J. P., Nelson R. B., Davis L. G. Expression of beta-amyloid precursor protein in reactive astrocytes following neuronal damage. Neuron. 1989 Sep;3(3):275–285. doi: 10.1016/0896-6273(89)90252-3. [DOI] [PubMed] [Google Scholar]
  36. Willoughby D. A., Johnson S. A., Pasinetti G. M., Tocco G., Najm I., Baudry M., Finch C. E. Amyloid precursor protein mRNA encoding the Kunitz protease inhibitor domain is increased by kainic acid-induced seizures in rat hippocampus. Exp Neurol. 1992 Dec;118(3):332–339. doi: 10.1016/0014-4886(92)90191-r. [DOI] [PubMed] [Google Scholar]
  37. van Duijn C. M., Stijnen T., Hofman A. Risk factors for Alzheimer's disease: overview of the EURODEM collaborative re-analysis of case-control studies. EURODEM Risk Factors Research Group. Int J Epidemiol. 1991;20 (Suppl 2):S4–12. doi: 10.1093/ije/20.supplement_2.s4. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Neurology, Neurosurgery, and Psychiatry are provided here courtesy of BMJ Publishing Group

RESOURCES