Journal of Neural Transmission

, Volume 112, Issue 11, pp 1547–1564 | Cite as

Traumatic brain injury: cause or risk of Alzheimer’s disease? A review of experimental studies

  • J. Szczygielski
  • A. Mautes
  • W. I. Steudel
  • P. Falkai
  • T.A. Bayer
  • O. Wirths


Traumatic Brain Injury is the leading cause of death and disability among young individuals in our society. Moreover, according to some epidemiological studies, head trauma is one of the most potent environmental risk factors for subsequent development of Alzheimer’s disease. Interestingly, pathological features that are present also in Alzheimer’s disease (in particular deposition of beta-amyloid protein) were observed in traumatised brains already a few hours after the initial insult. The primary objective of this review is to present methodology and results of numerous recent human and animal studies dealing with this issue. Special emphasis was placed on head trauma experiments in transgenic mouse models of Alzheimer’s disease. We further evaluate the connection between traumatic brain insults and subsequent development of dementia and try to differentiate between primary and secondary pathological mechanisms.

Keywords: Brain trauma, axonal injury, Alzheimer’s disease, transgenic mice, amyloid precursor protein. 


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  1. Abe, K, Tanzi, RE, Kogure, K 1991Selective induction of Kunitz-type protease inhibitor domain-containing amyloid precursor protein mRNA after persistent focal ischemia in rat cerebral cortex.Neurosci Lett125172174CrossRefPubMedGoogle Scholar
  2. Allsop, D, Haga, S, Bruton, C, Ishii, T, Roberts, GW 1990Neurofibrillary tangles in some cases of dementia pugilistic share antigens with amyloid beta-protein of Alzheimer10/19/05’s disease.Am J Pathol136255260PubMedGoogle Scholar
  3. Al-Sarraj, S, Hortobagyi, T, Wise, S 2004β-Amyloid precursor protein (βAPP) immunohistochemistry detects axonal injury in less than 60 minutes after human brain trauma.J Neurol Neurosurg Psychiatry63534Google Scholar
  4. Arnold, SE, Hyman, BT, Flory, J, Damasio, AR, Van Hoesen, GW 1991The topographical and neuroanatomical distribution of neurofibrillary tangles and neuritic plaques in the cerebral cortex of patients with Alzheimer’s disease.Cereb Cortex1103116PubMedGoogle Scholar
  5. Bacskai, BJ, Kajdasz, ST, Christie, RH, Carter, C, Games, D, Seubert, P, Schenk, D, Hyman, BT 2001Imaging of amyloid-beta deposits in brains of living mice permits direct observation of clearance of plaques with immunotherapy.Nat Med7369372CrossRefPubMedGoogle Scholar
  6. Bayer, TA, Wirths, O, Majtenyi, K, Hartmann, T, Multhaup, G, Beyreuther, K, Czech, C 2001Key factors in Alzheimer’s disease: beta-amyloid precursor protein processing, metabolism and intraneuronal transport.Brain Pathol11111PubMedGoogle Scholar
  7. Beeson, JG, Shelton, ER, Chan, HW, Gage, FH 1994Age and damage induced changes in amyloid protein precursor immunohistochemistry in the rat brain.J Comp Neurol3426977CrossRefPubMedGoogle Scholar
  8. Benveniste, H, Einstein, G, Kim, KR, Hulette, C, Johnson, GA 1999Detection of neuritic plaques in Alzheimer’s disease by magnetic resonance microscopy.Proc Natl Acad Sci USA961407914084CrossRefPubMedGoogle Scholar
  9. Blasko, I, Beer, R, Bigl, M, Apelt, J, Franz, G, Rudzki, D, Ransmayr, G, Kampfl, A, Schliebs, R 2004Experimental traumatic brain injury in rats stimulates the expression, production and activity of Alzheimer’s disease beta-secretase (BACE-1).J Neural Transm111523536CrossRefPubMedGoogle Scholar
  10. Blumbergs, PC, Scott, G, Manavis, J, Wainwright, H, Simpson, DA, McLean, AJ 1994Staining of amyloid precursor protein to study axonal damage in mild head injury.Lancet34410551056CrossRefPubMedGoogle Scholar
  11. Blumbergs, PC, Scott, G, Manavis, J, Wainwright, H, Simpson, DA, McLean, AJ 1995Topography of axonal injury as defined by amyloid precursor protein and the sector scoring method in mild and severe closed head injury.J Neurotrauma12565572PubMedGoogle Scholar
  12. Braak, H, Braak, E 1991Neuropathological stageing of Alzheimer-related changes.Acta Neuropathol (Berl)82239259CrossRefGoogle Scholar
  13. Bramlett, HM, Kraydieh, S, Green, EJ, Dietrich, WD 1997Temporal and regional patterns of axonal damage following traumatic brain injury: a beta-amyloid precursor protein immunocytochemical study in rats.J Neuropathol Exp Neurol5611321141PubMedGoogle Scholar
  14. Broe, GA, Henderson, AS, Creasey, H, McCusker, E, Korten, AE, Jorm, AF, Longley, W, Anthony, JC 1990A case-control study of Alzheimer’s disease in Australia.Neurology4016981707PubMedGoogle Scholar
  15. Bruns, J,Jr, Hauser, WA 2003The epidemiology of traumatic brain injury: a review.Epilepsia44210CrossRefGoogle Scholar
  16. Buxbaum, JD, Christensen, JL, Ruefli, AA, Greengard, P, Loring, JF 1993Expression of APP in brains of transgenic mice containing the entire human APP gene.Biochem Biophys Res Commun197639645CrossRefPubMedGoogle Scholar
  17. Buxbaum, JD, Thinakaran, G, Koliatsos, V, O’Callahan, J, Slunt, HH, Price, DL, Sisodia, SS 1998Alzheimer amyloid protein precursor in the rat hippocampus: transport and processing through the perforant path.J Neurosci1896299637PubMedGoogle Scholar
  18. Chandra, V, Kokmen, E, Schoenberg, BS, Beard, CM 1989Head trauma with loss of consciousness as a risk factor for Alzheimer’s disease.Neurology3915761578PubMedGoogle Scholar
  19. Chen, XH, Siman, R, Iwata, A, Meaney, DF, Trojanowski, JQ, Smith, DH 2004Long-term accumulation of amyloid-{beta}, {beta}-secretase, presenilin-1, and caspase-3 in damaged axons following brain trauma.Am J Pathol165357371PubMedGoogle Scholar
  20. Ciallella, JR, Ikonomovic, MD, Paljug, WR, Wilbur, YI, Dixon, CE, Kochanek, PM, Marion, DW, DeKosky, ST 2002Changes in expression of amyloid precursor protein and interleukin-1beta after experimental traumatic brain injury in rats.J Neurotrauma1915551567CrossRefPubMedGoogle Scholar
  21. Clinton, J, Ambler, MW, Roberts, GW 1991Post-traumatic Alzheimer’s disease: preponderance of a single plaque type.Neuropathol Appl Neurobiol176974PubMedGoogle Scholar
  22. Cornish, R, Blumbergs, PC, Manavis, J, Scott, G, Jones, NR, Reilly, PL 2000Topography and severity of axonal injury in human spinal cord trauma using amyloid precursor protein as a marker of axonal injury.Spine2512271233CrossRefPubMedGoogle Scholar
  23. Emmerling, MR, Morganti-Kossmann, MC, Kossmann, T, Stahel, PF, Watson, MD, Evans, LM, Mehta, PD, Spiegel, K, Kuo, YM, Roher, AE, Raby, CA 2000Traumatic brain injury elevates the Alzheimer’s amyloid peptide A beta 42 in human CSF. A possible role for nerve cell injury.Ann NY Acad Sci903118122PubMedGoogle Scholar
  24. Fleminger, S, Oliver, DL, Lovestone, S, Rabe-Hesketh, S, Giora, A 2003Head injury as a risk factor for Alzheimer’s disease: the evidence 10 years on; a partial replication.J Neurol Neurosurg Psychiatry74857862CrossRefPubMedGoogle Scholar
  25. Franz, G, Beer, R, Kampfl, A, Engelhardt, K, Schmutzhard, E, Ulmer, H, Deisenhammer, F 2003Amyloid beta 1–42 and tau in cerebrospinal fluid after severe traumatic brain injury.Neurology6014571461PubMedGoogle Scholar
  26. Gallant, PE 1992The direct effects of graded axonal compression on axoplasm and fast axoplasmic transport.J Neuropathol Exp Neurol51220230PubMedGoogle Scholar
  27. Geddes, JF, Vowles, GH, Beer, TW, Ellison, DW 1997The diagnosis of diffuse axonal injury: implications for forensic practice.Neuropathol Appl Neurobiol23339347CrossRefPubMedGoogle Scholar
  28. Geddes, JF, Vowles, GH, Nicoll, JA, Revesz, T 1999Neuronal cytoskeletal changes are an early consequence of repetitive head injury.Acta Neuropathol (Berl)98171178CrossRefGoogle Scholar
  29. Geddes, JF, Vowles, GH, Robinson, SF, Sutcliffe, JC 1996Neurofibrillary tangles, but not Alzheimer-type pathology, in a young boxer.Neuropathol Appl Neurobiol221216CrossRefPubMedGoogle Scholar
  30. Geddes, JF, Whitwell, HL, Graham, DI 2000Traumatic axonal injury: practical issues for diagnosis in medicolegal cases.Neuropathol Appl Neurobiol26105116CrossRefPubMedGoogle Scholar
  31. Genis, L, Chen, Y, Shohami, E, Michaelson, DM 2000Tau hyperphosphorylation in apolipoprotein E-deficient and control mice after closed head injury.J Neurosci Res60559564CrossRefPubMedGoogle Scholar
  32. Gennarelli, TA, Tipperman, R, Maxwell, WL, Graham, DI, Adams, JH, Irvine, A 1993Traumatic damage to the nodal axolemma: an early, secondary injury.Acta Neurochir (Wien) (Suppl)574952Google Scholar
  33. Gentleman, SM, Graham, DI, Roberts, GW 1993aMolecular pathology of head trauma: altered beta APP metabolism and the aetiology of Alzheimer’s disease.Prog Brain Res96237246Google Scholar
  34. Gentleman, SM, Nash, MJ, Sweeting, CJ, Graham, DI, Roberts, GW 1993bBeta-amyloid precursor protein (beta APP) as a marker for axonal injury after head injury.Neurosci Lett160139144CrossRefGoogle Scholar
  35. Gentleman, SM, Leclercq, PD, Moyes, L, Graham, DI, Smith, C, Griffin, WS, Nicoll, JA 2004Long-term intracerebral inflammatory response after traumatic brain injury.Forensic Sci Int14697104CrossRefPubMedGoogle Scholar
  36. Gentleman, SM, Roberts, GW, Gennarelli, TA, Maxwell, WL, Adams, JH, Kerr, S, Graham, DI 1995Axonal injury: a universal consequence of fatal closed head injury?Acta Neuropathol (Berl)89537543Google Scholar
  37. Gottlieb, S 2000Head injury doubles the risk for Alzheimer’s disease.Br Med J3211100Google Scholar
  38. Graham, DI, Gentleman, SM, Nicoll, JA, Royston, MC, McKenzie, JE, Roberts, GW, Griffin, WS 1996Altered beta-APP metabolism after head injury and its relationship to the aetiology of Alzheimer’s disease.Acta Neurochir (Wien) (Suppl)6696102Google Scholar
  39. Griffin, WS, Sheng, JG, Gentleman, SM, Graham, DI, Mrak, RE, Roberts, GW 1994Microglial interleukin-1 alpha expression in human head injury: correlations with neuronal and neuritic beta-amyloid precursor protein expression.Neurosci Lett176133136CrossRefPubMedGoogle Scholar
  40. Hamberger, A, Huang, YL, Zhu, H, Bao, F, Ding, M, Blennow, K, Olsson, A, Hansson, HA, Viano, D, Haglid, KG 2003Redistribution of neurofilaments and accumulation of beta-amyloid protein after brain injury by rotational acceleration of the head.J Neurotrauma20169178CrossRefPubMedGoogle Scholar
  41. Hardy, JA, Higgins, GA 1992Alzheimer’s disease: the amyloid cascade hypothesis.Science256184185PubMedGoogle Scholar
  42. Hartman, RE, Laurer, H, Longhi, L, Bales, KR, Paul, SM, McIntosh, TK, Holtzman, DM 2002Apolipoprotein E4 influences amyloid deposition but not cell loss after traumatic brain injury in a mouse model of Alzheimer’s disease.J Neurosci221008310087PubMedGoogle Scholar
  43. Heurteaux, C, Bertaina, V, Widmann, C, Lazdunski, M 1993K+ channel openers prevent global ischemia-induced expression of c-fos, c-jun, heat shock protein, and amyloid beta-protein precursor genes and neuronal death in rat hippocampus.Proc Natl Acad Sci USA9094319435PubMedGoogle Scholar
  44. Hoshino, S, Kobayashi, S, Furukawa, T, Asakura, T, Teramoto, A 2003Multiple immunostaining methods to detect traumatic axonal injury in the rat fluid-percussion brain injury model.Neurol Med Chir (Tokyo)43165173discussion 174CrossRefGoogle Scholar
  45. Hoshino, S, Tamaoka, A, Takahashi, M, Kobayashi, S, Furukawa, T, Oaki, Y, Mori, O, Matsuno, S, Shoji, S, Inomata, M, Teramoto, A 1998Emergence of immunoreactivities for phosphorylated tau and amyloid-beta protein in chronic stage of fluid percussion injury in rat brain.Neuroreport918791883PubMedGoogle Scholar
  46. Huber, A, Gabbert, K, Keleman, J, Cervos-Navarro, J 1990Density of amyloid plaques in brain after head trauma.J Neurotrauma(Suppl 1)S180Google Scholar
  47. Iino, M, Nakatome, M, Ogura, Y, Fujimura, H, Kuroki, H, Inoue, H, Ino, Y, Fujii, T, Terao, T, Matoba, R 2003Real-time PCR quantitation of FE65 a beta-amyloid precursor protein-binding protein after traumatic brain injury in rats.Int J Legal Med117153159PubMedGoogle Scholar
  48. Ikonomovic, MD, Uryu, K, Abrahamson, EE, Ciallella, JR, Trojanowski, JQ, Lee, VM, Clark, RS, Marion, DW, Wisniewski, SR, DeKosky, ST 2004Alzheimer’s pathology in human temporal cortex surgically excised after severe brain injury.Exp Neurol190192203CrossRefPubMedGoogle Scholar
  49. Irving, EA, Bentley, DL, Parsons, AA 2001Assessment of white matter injury following prolonged focal cerebral ischaemia in the rat.Acta Neuropathol (Berl)102627635Google Scholar
  50. Irving, EA, Nicoll, J, Graham, DI, Dewar, D 1996Increased tau immunoreactivity in oligodendrocytes following human stroke and head injury.Neurosci Lett213189192PubMedGoogle Scholar
  51. Iwata, A, Chen, XH, McIntosh, TK, Browne, KD, Smith, D 2002Long-term accumulation of amyloid-beta in axons following brain trauma without persistent upregulation of amyloid precursor protein genes.J Neuropathol Exp Neurol6110561068PubMedGoogle Scholar
  52. Jellinger, KA 2004Traumatic brain injury as a risk factor for Alzheimer’s disease.J Neurol Neurosurg Psychiatry75511512Google Scholar
  53. Kalaria, RN, Bhatti, SU, Lust, WD, Perry, G 1993The amyloid precursor protein in ischemic brain injury and chronic hypoperfusion.Ann NY Acad Sci695190193PubMedGoogle Scholar
  54. Kawarabayashi, T, Shoji, M, Harigaya, Y, Yamaguchi, H, Hirai, S 1991Expression of APP in the early stage of brain damage.Brain Res563334338CrossRefPubMedGoogle Scholar
  55. Kim, HS, Lee, SH, Kim, SS, Kim, YK, Jeong, SJ, Ma, J, Han, DH, Cho, BK, Suh, YH 1998Post-ischemic changes in the expression of Alzheimer’s APP isoforms in rat cerebral cortex.Neuroreport9533537PubMedGoogle Scholar
  56. Koistinaho, J, Pyykonen, I, Keinanen, R, Hokfelt, T 1996Expression of beta-amyloid precursor protein mRNAs following transient focal ischaemia.Neuroreport727272731PubMedGoogle Scholar
  57. Koo, EH, Sisodia, SS, Archer, DR, Martin, LJ, Weidemann, A, Beyreuther, K, Fischer, P, Masters, CL, Price, DL 1990Precursor of amyloid protein in Alzheimer disease undergoes fast anterograde axonal transport.Proc Natl Acad Sci USA8715611565PubMedGoogle Scholar
  58. Kung, MP, Zhuang, ZP, Hou, C, Kung, HF 2004Development and evaluation of iodinated tracers targeting amyloid plaques for SPECT imaging.J Mol Neurosci244954CrossRefPubMedGoogle Scholar
  59. Lambri, M, Djurovic, V, Kibble, M, Cairns, N, Al-Sarraj, S 2001Specificity and sensitivity of betaAPP in head injury.Clin Neuropathol20263271PubMedGoogle Scholar
  60. Laurer, HL, Bareyre, FM, Lee, VM, Trojanowski, JQ, Longhi, L, Hoover, R, Saatman, KE, Raghupathi, R, Hoshino, S, Grady, MS, McIntosh, TK 2001Mild head injury increasing the brain’s vulnerability to a second concussive impact.J Neurosurg95859870PubMedGoogle Scholar
  61. Lee, SP, Falangola, MF, Nixon, RA, Duff, K, Helpern, JA 2004Visualization of beta-amyloid plaques in a transgenic mouse model of Alzheimer’s disease using MR microscopy without contrast reagents.Magn Reson Med52538544CrossRefPubMedGoogle Scholar
  62. Lewen, A, Li, GL, Nilsson, P, Olsson, Y, Hillered, L 1995Traumatic brain injury in rat produces changes of beta-amyloid precursor protein immunoreactivity.Neuroreport6357360PubMedGoogle Scholar
  63. Lewen, A, Li, GL, Olsson, Y, Hillered, L 1996Changes in microtubule-associated protein 2 and amyloid precursor protein immunoreactivity following traumatic brain injury in rat: influence of MK-801 treatment.Brain Res719161171CrossRefPubMedGoogle Scholar
  64. Lin, L, LeBlanc, CJ, Deacon, TW, Isacson, O 1998Chronic cognitive deficits and amyloid precursor protein elevation after selective immunotoxin lesions of the basal forebrain cholinergic system.Neuroreport9547552PubMedGoogle Scholar
  65. Lye, TC, Shores, EA 2000Traumatic brain injury as a risk factor for Alzheimer’s disease: a review.Neuropsychol Rev10115129CrossRefPubMedGoogle Scholar
  66. Macfarlane, DP, Nicoll, JA, Smith, C, Graham, DI 1999APOE epsilon4 allele and amyloid beta-protein deposition in long term survivors of head injury.Neuroreport1039453948PubMedGoogle Scholar
  67. Masumura, M, Hata, R, Uramoto, H, Murayama, N, Ohno, T, Sawada, T 2000Altered expression of amyloid precursors proteins after traumatic brain injury in rats: in situ hybridization and immunohistochemical study.J Neurotrauma17123134PubMedGoogle Scholar
  68. Maxwell, WL, McCreath, BJ, Graham, DI, Gennarelli, TA 1995Cytochemical evidence for redistribution of membrane pump calcium-ATPase and ecto-Ca-ATPase activity, and calcium influx in myelinated nerve fibres of the optic nerve after stretch injury.J Neurocytol24925942CrossRefPubMedGoogle Scholar
  69. Maxwell, WL, Povlishock, JT, Graham, DL 1997A mechanistic analysis of nondisruptive axonal injury: a review.J Neurotrauma14419440PubMedGoogle Scholar
  70. Maxwell, WL, Watt, C, Graham, DI, Gennarelli, TA 1993Ultrastructural evidence of axonal shearing as a result of lateral acceleration of the head in non-human primates.Acta Neuropathol (Berl)86136144CrossRefGoogle Scholar
  71. McKenzie, JE, Gentleman, SM, Roberts, GW, Graham, DI, Royston, MC 1994Increased numbers of beta APP-immunoreactive neurones in the entorhinal cortex after head injury.Neuroreport6161164PubMedGoogle Scholar
  72. McKenzie, KJ, McLellan, DR, Gentleman, SM, Maxwell, WL, Gennarelli, TA, Graham, DI 1996Is beta-APP a marker of axonal damage in short-surviving head injury?Acta Neuropathol (Berl)92608613CrossRefGoogle Scholar
  73. Mehta, KM, Ott, A, Kalmijn, S, Slooter, AJ, van Duijn, CM, Hofman, A, Breteler, MM 1999Head trauma and risk of dementia and Alzheimer’s disease: The Rotterdam Study.Neurology5319591962PubMedGoogle Scholar
  74. Morin, PJ, Abraham, CR, Amaratunga, A, Johnson, RJ, Huber, G, Sandell, JH, Fine, RE 1993Amyloid precursor protein is synthesized by retinal ganglion cells, rapidly transported to the optic nerve plasma membrane and nerve terminals, and metabolized.J Neurochem61464473PubMedGoogle Scholar
  75. Murai, H, Pierce, JE, Raghupathi, R, Smith, DH, Saatman, KE, Trojanowski, JQ, Lee, VM, Loring, JF, Eckman, C, Younkin, S, McIntosh, TK 1998Twofold overexpression of human beta-amyloid precursor proteins in transgenic mice does not affect the neuromotor, cognitive, or neurodegenerative sequelae following experimental brain injury.J Comp Neurol392428438CrossRefPubMedGoogle Scholar
  76. Murakami, N, Yamaki, T, Iwamoto, Y, Sakakibara, T, Kobori, N, Fushiki, S, Ueda, S 1998Experimental brain injury induces expression of amyloid precursor protein, which may be related to neuronal loss in the hippocampus.J Neurotrauma159931003PubMedGoogle Scholar
  77. Nakagawa, Y, Nakamura, M, McIntosh, TK, Rodriguez, A, Berlin, JA, Smith, DH, Saatman, KE, Raghupathi, R, Clemens, J, Saido, TC, Schmidt, ML, Lee, VM, Trojanowski, JQ 1999Traumatic brain injury in young, amyloid-beta peptide overexpressing transgenic mice induces marked ipsilateral hippocampal atrophy and diminished Abeta deposition during aging.J Comp Neurol411390398CrossRefPubMedGoogle Scholar
  78. Nakagawa, Y, Reed, L, Nakamura, M, McIntosh, TK, Smith, DH, Saatman, KE, Raghupathi, R, Clemens, J, Saido, TC, Lee, VM, Trojanowski, JQ 2000Brain trauma in aged transgenic mice induces regression of established abeta deposits.Exp Neurol163244252CrossRefPubMedGoogle Scholar
  79. Niess, C, Grauel, U, Toennes, SW, Bratzke, H 2002Incidence of axonal injury in human brain tissue.Acta Neuropathol (Berl)1047984CrossRefGoogle Scholar
  80. Nunan, J, Small, DH 2000Regulation of APP cleavage by alpha-, beta- and gamma-secretases.FEBS Lett483610CrossRefPubMedGoogle Scholar
  81. Ohgami, T, Kitamoto, T, Tateishi, J 1992Alzheimer’s amyloid precursor protein accumulates within axonal swellings in human brain lesions.Neurosci Lett1367578CrossRefPubMedGoogle Scholar
  82. Olsson, A, Csajbok, L, Ost, M, Hoglund, K, Nylen, K, Rosengren, L, Nellgard, B, Blennow, K 2004Marked increase of beta-amyloid ((1–42)) and amyloid precursor protein in ventricular cerebrospinal fluid after severe traumatic brain injury.J Neurol251870876CrossRefPubMedGoogle Scholar
  83. Otsuka, N, Tomonaga, M, Ikeda, K 1991Rapid appearance of beta-amyloid precursor protein immunoreactivity in damaged axons and reactive glial cells in rat brain following needle stab injury.Brain Res568335338CrossRefPubMedGoogle Scholar
  84. Palacios, G, Palacios, JM, Mengod, G, Frey, P 1992Beta-amyloid precursor protein localization in the Golgi apparatus in neurons and oligodendrocytes. An immunocytochemical structural and ultrastructural study in normal and axotomized neurons.Brain Res Mol Brain Res15195206CrossRefPubMedGoogle Scholar
  85. Pettus, EH, Christman, CW, Giebel, ML, Povlishock, JT 1994Traumatically induced altered membrane permeability: its relationship to traumatically induced reactive axonal change.J Neurotrauma11507522PubMedGoogle Scholar
  86. Pettus, EH, Povlishock, JT 1996Characterization of a distinct set of intra-axonal ultrastructural changes associated with traumatically induced alteration in axolemmal permeability.Brain Res722111CrossRefPubMedGoogle Scholar
  87. Pierce, JE, Trojanowski, JQ, Graham, DI, Smith, DH, McIntosh, TK 1996Immunohistochemical characterization of alterations in the distribution of amyloid precursor proteins and beta-amyloid peptide after experimental brain injury in the rat.J Neurosci1610831090PubMedGoogle Scholar
  88. Plassman, BL, Havlik, RJ, Steffens, DC, Helms, MJ, Newman, TN, Drosdick, D, Phillips, C, Gau, BA, Welsh-Bohmer, KA, Burke, JR, Guralnik, JM, Breitner, JC 2000Documented head injury in early adulthood and risk of Alzheimer’s disease and other dementias.Neurology5511581166PubMedGoogle Scholar
  89. Pluta, R, Kida, E, Lossinsky, AS, Golabek, AA, Mossakowski, MJ, Wisniewski, HM 1994Complete cerebral ischemia with short-term survival in rats induced by cardiac arrest. I. Extracellular accumulation of Alzheimer’s beta-amyloid protein precursor in the brain.Brain Res649323328CrossRefPubMedGoogle Scholar
  90. Povlishock, JT 1993Pathobiology of traumatically induced axonal injury in animals and man.Ann Emerg Med22980986CrossRefPubMedGoogle Scholar
  91. Povlishock, JT, Marmarou, A, McIntosh, T, Trojanowski, JQ, Moroi, J 1997Impact acceleration injury in the rat: evidence for focal axolemmal change and related neurofilament sidearm alteration.J Neuropathol Exp Neurol56347359PubMedGoogle Scholar
  92. Reichard, RR, White, CL,3rd, Hladik, CL, Dolinak, D 2003Beta-amyloid precursor protein staining of nonaccidental central nervous system injury in pediatric autopsies.J Neurotrauma20347355CrossRefPubMedGoogle Scholar
  93. Reichard, RR, White, CL,3rd, Hogan, RN, Hladik, CL, Dolinak, D 2004Beta-amyloid precursor protein immunohistochemistry in the evaluation of pediatric traumatic optic nerve injury.Ophthalmology111822827CrossRefPubMedGoogle Scholar
  94. Roberts, GW, Allsop, D, Bruton, C 1990The occult aftermath of boxing.J Neurol Neurosurg Psychiatry53373378PubMedGoogle Scholar
  95. Roberts, GW, Gentleman, SM, Lynch, A, Graham, DI 1991beta A4 amyloid protein deposition in brain after head trauma.Lancet33814221423CrossRefPubMedGoogle Scholar
  96. Roberts, GW, Gentleman, SM, Lynch, A, Murray, L, Landon, M, Graham, DI 1994Beta amyloid protein deposition in the brain after severe head injury: implications for the pathogenesis of Alzheimer’s disease.J Neurol Neurosurg Psychiatry57419425PubMedGoogle Scholar
  97. Schmechel, DE, Goldgaber, D, Burkhart, DS, Gilbert, JR, Gajdusek, DC, Roses, AD 1988Cellular localization of messenger RNA encoding amyloid-beta-protein in normal tissue and in Alzheimer disease.Alzheimer Dis Assoc Disord296111PubMedGoogle Scholar
  98. Schmidt, ML, Zhukareva, V, Newell, KL, Lee, VM, Trojanowski, JQ 2001Tau isoform profile and phosphorylation state in dementia pugilistica recapitulate Alzheimer’s disease.Acta Neuropathol (Berl)101518524Google Scholar
  99. Schmitz, C, Rutten, BP, Pielen, A, Schafer, S, Wirths, O, Tremp, G, Czech, C, Blanchard, V, Multhaup, G, Rezaie, P, Korr, H, Steinbusch, HW, Pradier, L, Bayer, TA 2004Hippocampal neuron loss exceeds amyloid plaque load in a transgenic mouse model of Alzheimer’s disease.Am J Pathol16414951502PubMedGoogle Scholar
  100. Scott, JN, Parhad, IM, Clark, AW 1991Beta-amyloid precursor protein gene is differentially expressed in axotomized sensory and motor systems.Brain Res Mol Brain Res10315325CrossRefPubMedGoogle Scholar
  101. Selkoe, DJ 2001Alzheimer’s disease: genes proteins, and therapy.Physiol Rev81741766PubMedGoogle Scholar
  102. Seubert, P, Oltersdorf, T, Lee, MG, Barbour, R, Blomquist, C, Davis, DL, Btyany, K, Fritz, LC, Glasko, D, Thal, LJ, Lieberburg, I, Schenk, DB 1993Secretion of beta-amyloid precursor protein cleaved at the amino-terminus of the beta-amyloid peptide.Nature361260263CrossRefPubMedGoogle Scholar
  103. Sherriff, FE, Bridges, LR, Gentleman, SM, Sivaloganathan, S, Wilson, S 1994Markers of axonal injury in post mortem human brain.Acta Neuropathol (Berl)88433439Google Scholar
  104. Sherriff, FE, Bridges, LR, Sivaloganathan, S 1994Early detection of axonal injury after human head trauma using immunocytochemistry for beta-amyloid precursor protein.Acta Neuropathol (Berl)875562Google Scholar
  105. Shigematsu, K, McGeer, PL 1992Accumulation of amyloid precursor protein in neurons after intraventricular injection of colchicine.Am J Pathol140787794PubMedGoogle Scholar
  106. Shoghi-Jadid, K, Small, GW, Agdeppa, ED, Kepe, V, Ercoli, LM, Siddarth, P, Read, S, Satyamurthy, N, Petric, A, Huang, SC, Barrio, JR 2002Localization of neurofibrillary tangles and beta-amyloid plaques in the brains of living patients with Alzheimer disease.Am J Geriatr Psychiatry102435CrossRefPubMedGoogle Scholar
  107. Siman, R, Card, JP, Nelson, RB, Davis, LG 1989Expression of beta-amyloid precursor protein in reactive astrocytes following neuronal damage.Neuron3275285CrossRefPubMedGoogle Scholar
  108. Sisodia, SS, Koo, EH, Hoffman, PN, Perry, G, Price, DL 1993Identification and transport of full-length amyloid precursor proteins in rat peripheral nervous system.J Neurosci1331363142PubMedGoogle Scholar
  109. Smith, C, Graham, DI, Murray, LS, Nicoll, JA 2003Tau immunohistochemistry in acute brain injury.Neuropathol Appl Neurobiol29496502CrossRefPubMedGoogle Scholar
  110. Smith, DH, Chen, XH, Iwata, A, Graham, DI 2003Amyloid beta accumulation in axons after traumatic brain injury in humans.J Neurosurg9810721077PubMedGoogle Scholar
  111. Smith, DH, Chen, XH, Nonaka, M, Trojanowski, JQ, Lee, VM, Saatman, KE, Leoni, MJ, Xu, BN, Wolf, JA, Meaney, DF 1999Accumulation of amyloid beta and tau and the formation of neurofilament inclusions following diffuse brain injury in the pig.J Neuropathol Exp Neurol58982992PubMedGoogle Scholar
  112. Smith, DH, Meaney, DF 2000Axonal damage in traumatic brain injury.Neuroscientist6483495Google Scholar
  113. Smith, DH, Nakamura, M, McIntosh, TK, Wang, J, Rodriguez, A, Chen, XH, Raghupathi, R, Saatman, KE, Clemens, J, Schmidt, ML, Lee, VM, Trojanowski, JQ 1998Brain trauma induces massive hippocampal neuron death linked to a surge in beta-amyloid levels in mice overexpressing mutant amyloid precursor protein.Am J Pathol15310051010PubMedGoogle Scholar
  114. Stephenson, DT, Rash, K, Clemens, JA 1992Amyloid precursor protein accumulates in regions of neurodegeneration following focal cerebral ischemia in the rat.Brain Res593128135CrossRefPubMedGoogle Scholar
  115. Stone, JR, Walker, SA, Povlishock, JT 1999The visualization of a new class of traumatically injured axons through the use of a modified method of microwave antigen retrieval.Acta Neuropathol (Berl)97335345CrossRefGoogle Scholar
  116. Tokuda, T, Ikeda, S, Yanagisawa, N, Ihara, Y, Glenner, GG 1991Re-examination of ex-boxers’ brains using immunohistochemistry with antibodies to amyloid beta-protein and tau protein.Acta Neuropathol (Berl)82280285CrossRefGoogle Scholar
  117. Turner, PR, O’Connor, K, Tate, WP, Abraham, WC 2003Roles of amyloid precursor protein and its fragments in regulating neural activity, plasticity and memory.Prog Neurobiol70132CrossRefPubMedGoogle Scholar
  118. Uryu, K, Laurer, H, McIntosh, T, Pratico, D, Martinez, D, Leight, S, Lee, VM, Trojanowski, JQ 2002Repetitive mild brain trauma accelerates Abeta deposition, lipid peroxidation, and cognitive impairment in a transgenic mouse model of Alzheimer amyloidosis.J Neurosci22446454PubMedGoogle Scholar
  119. Van Den Heuvel, C, Blumbergs, P, Finnie, J, Manavis, J, Lewis, S, Jones, N, Reilly, P, Pereira, R 2000Upregulation of amyloid precursor protein and its mRNA in an experimental model of paediatric head injury.J Clin Neurosci7140145CrossRefPubMedGoogle Scholar
  120. Van Den Heuvel, C, Blumbergs, PC, Finnie, JW, Manavis, J, Jones, NR, Reilly, PL, Pereira, RA 1999Upregulation of amyloid precursor protein messenger RNA in response to traumatic brain injury: an ovine head impact model.Exp Neurol159441450CrossRefPubMedGoogle Scholar
  121. Van Den Heuvel, C, Lewis, S, Wong, M, Manavis, J, Finnie, J, Blumbergs, P, Jones, N, Reilly, P 1998Diffuse neuronal perikaryon amyloid precursor protein immunoreactivity in a focal head impact model.Acta Neurochir (Wien) (Suppl)71209211Google Scholar
  122. Wallace, WC, Bragin, V, Robakis, NK, Sambamurti, K, VanderPutten, D, Merril, CR, Davis, KL, Santucci, AC, Haroutunian, V 1991Increased biosynthesis of Alzheimer amyloid precursor protein in the cerebral cortex of rats with lesions of the nucleus basalis of Meynert.Brain Res Mol Brain Res10173178CrossRefPubMedGoogle Scholar
  123. Wilkinson, AE, Bridges, LR, Sivaloganathan, S 1999Correlation of survival time with size of axonal swellings in diffuse axonal injury.Acta Neuropathol (Berl)98197202CrossRefGoogle Scholar
  124. Wirths, O, Multhaup, G, Bayer, TA 2004A modified beta-amyloid hypothesis: intraneuronal accumulation of the beta-amyloid peptide – the first step of a fatal cascade.J Neurochem91513520CrossRefPubMedGoogle Scholar
  125. Yam, PS, Takasago, T, Dewar, D, Graham, DI, McCulloch, J 1997Amyloid precursor protein accumulates in white matter at the margin of a focal ischaemic lesion.Brain Res760150157CrossRefPubMedGoogle Scholar
  126. Zemlan, FP, Jauch, EC, Mulchahey, JJ, Gabbita, SP, Rosenberg, WS, Speciale, SG, Zuccarello, M 2002C-tau biomarker of neuronal damage in severe brain injured patients: association with elevated intracranial pressure and clinical outcome.Brain Res947131139CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag/Wien 2005

Authors and Affiliations

  • J. Szczygielski
    • 2
    • 3
  • A. Mautes
    • 3
  • W. I. Steudel
    • 3
  • P. Falkai
    • 1
  • T.A. Bayer
    • 1
    • 2
  • O. Wirths
    • 1
    • 2
  1. 1.Department of PsychiatrySaarland UniversityHomburgGermany
  2. 2.Section NeurobiologySaarland UniversityHomburgGermany
  3. 3.Department of NeurosurgerySaarland UniversityHomburgGermany

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