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J Neurol Neurosurg Psychiatry. Apr 1994; 57(4): 419–425.
PMCID: PMC1072869

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

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.

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  • Adams JH, Doyle D, Graham DI, Lawrence AE, McLellan DR, Gennarelli TA, 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. [PubMed]
  • Adams JH, Doyle D, Ford I, Gennarelli TA, Graham DI, McLellan DR. Diffuse axonal injury in head injury: definition, diagnosis and grading. Histopathology. 1989 Jul;15(1):49–59. [PubMed]
  • Graham DI, Ford I, Adams JH, Doyle D, Teasdale GM, Lawrence AE, McLellan DR. Ischaemic brain damage is still common in fatal non-missile head injury. J Neurol Neurosurg Psychiatry. 1989 Mar;52(3):346–350. [PMC free article] [PubMed]
  • Corsellis JA, Bruton CJ, Freeman-Browne D. The aftermath of boxing. Psychol Med. 1973 Aug;3(3):270–303. [PubMed]
  • Dale GE, Leigh PN, Luthert P, Anderton BH, Roberts GW. Neurofibrillary tangles in dementia pugilistica are ubiquitinated. J Neurol Neurosurg Psychiatry. 1991 Feb;54(2):116–118. [PMC free article] [PubMed]
  • Allsop D, Haga S, Bruton C, Ishii T, Roberts GW. 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]
  • Roberts GW. Immunocytochemistry of neurofibrillary tangles in dementia pugilistica and Alzheimer's disease: evidence for common genesis. Lancet. 1988 Dec 24;2(8626-8627):1456–1458. [PubMed]
  • Clinton J, Ambler MW, Roberts GW. Post-traumatic Alzheimer's disease: preponderance of a single plaque type. Neuropathol Appl Neurobiol. 1991 Feb;17(1):69–74. [PubMed]
  • Roberts GW, Whitwell HL, Acland PR, Bruton CJ. Dementia in a punch-drunk wife. Lancet. 1990 Apr 14;335(8694):918–919. [PubMed]
  • Roberts GW, Gentleman SM, Lynch A, Graham DI. beta A4 amyloid protein deposition in brain after head trauma. Lancet. 1991 Dec 7;338(8780):1422–1423. [PubMed]
  • Amaducci LA, Fratiglioni L, Rocca WA, Fieschi C, Livrea P, Pedone D, Bracco L, Lippi A, Gandolfo C, Bino G, et al. Risk factors for clinically diagnosed Alzheimer's disease: a case-control study of an Italian population. Neurology. 1986 Jul;36(7):922–931. [PubMed]
  • French LR, Schuman LM, Mortimer JA, Hutton JT, Boatman RA, Christians B. A case-control study of dementia of the Alzheimer type. Am J Epidemiol. 1985 Mar;121(3):414–421. [PubMed]
  • Rudelli R, Strom JO, Welch PT, Ambler MW. Posttraumatic premature Alzheimer's disease. Neuropathologic findings and pathogenetic considerations. Arch Neurol. 1982 Sep;39(9):570–575. [PubMed]
  • 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. [PubMed]
  • Royston MC, Rothwell NJ, Roberts GW. Alzheimer's disease: pathology to potential treatments? Trends Pharmacol Sci. 1992 Apr;13(4):131–133. [PubMed]
  • Davies L, Wolska B, Hilbich C, Multhaup G, Martins R, Simms G, Beyreuther K, Masters CL. 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. [PubMed]
  • Gentleman SM, Bruton C, Allsop D, Lewis SJ, Polak JM, Roberts GW. A demonstration of the advantages of immunostaining in the quantification of amyloid plaque deposits. Histochemistry. 1989;92(4):355–358. [PubMed]
  • Hardy J. Framing beta-amyloid. Nat Genet. 1992 Jul;1(4):233–234. [PubMed]
  • Gentleman SM, Graham DI, Roberts GW. Molecular pathology of head trauma: altered beta APP metabolism and the aetiology of Alzheimer's disease. Prog Brain Res. 1993;96:237–246. [PubMed]
  • Gautrin D, Gauthier S. Alzheimer's disease: environmental factors and etiologic hypotheses. Can J Neurol Sci. 1989 Nov;16(4):375–387. [PubMed]
  • Gentleman S, Roberts G. Risk factors in Alzheimer's disease. BMJ. 1992 Jan 11;304(6819):118–119. [PMC free article] [PubMed]
  • Shedden PM, Moulton RJ, Sullivan I, Hotz G, Tucker WS, Muller PJ. Effect of population characteristics on head injury mortality. Pediatr Neurosurg. 1990;16(4-5):203–207. [PubMed]
  • van Duijn CM, 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. [PubMed]
  • Roberts GW, Nash M, Ince PG, Royston MC, Gentleman SM. On the origin of Alzheimer's disease: a hypothesis. Neuroreport. 1993 Jan;4(1):7–9. [PubMed]
  • Gentleman SM, Nash MJ, Sweeting CJ, Graham DI, Roberts GW. Beta-amyloid precursor protein (beta APP) as a marker for axonal injury after head injury. Neurosci Lett. 1993 Oct 1;160(2):139–144. [PubMed]
  • Schubert W, Prior R, Weidemann A, Dircksen H, Multhaup G, Masters CL, 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. [PubMed]
  • 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. [PubMed]
  • 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. [PubMed]
  • Siman R, Card JP, Nelson RB, Davis LG. Expression of beta-amyloid precursor protein in reactive astrocytes following neuronal damage. Neuron. 1989 Sep;3(3):275–285. [PubMed]
  • Abe K, Tanzi RE, 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. [PubMed]
  • Willoughby DA, Johnson SA, Pasinetti GM, Tocco G, Najm I, Baudry M, Finch CE. 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. [PubMed]
  • Scott JN, Parhad IM, Clark AW. 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. [PubMed]
  • 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. [PubMed]
  • Seubert P, Vigo-Pelfrey C, Esch F, Lee M, Dovey H, Davis D, Sinha S, Schlossmacher M, Whaley J, Swindlehurst C, et al. Isolation and quantification of soluble Alzheimer's beta-peptide from biological fluids. Nature. 1992 Sep 24;359(6393):325–327. [PubMed]
  • Shoji M, Golde TE, Ghiso J, Cheung TT, Estus S, Shaffer LM, Cai XD, McKay DM, Tintner R, Frangione B, et al. Production of the Alzheimer amyloid beta protein by normal proteolytic processing. Science. 1992 Oct 2;258(5079):126–129. [PubMed]
  • McGeer PL, Rogers J. Anti-inflammatory agents as a therapeutic approach to Alzheimer's disease. Neurology. 1992 Feb;42(2):447–449. [PubMed]
  • Dinarello CA, Wolff SM. The role of interleukin-1 in disease. N Engl J Med. 1993 Jan 14;328(2):106–113. [PubMed]

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