Skip to main content

Advertisement

Log in

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

  • Review
  • Published:
Journal of Neural Transmission Aims and scope Submit manuscript

Summary.

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  • K Abe RE Tanzi K Kogure (1991) ArticleTitleSelective induction of Kunitz-type protease inhibitor domain-containing amyloid precursor protein mRNA after persistent focal ischemia in rat cerebral cortex. Neurosci Lett 125 172–174 Occurrence Handle10.1016/0304-3940(91)90020-T Occurrence Handle1908958

    Article  PubMed  Google Scholar 

  • D Allsop S Haga C Bruton T Ishii GW Roberts (1990) ArticleTitleNeurofibrillary tangles in some cases of dementia pugilistic share antigens with amyloid beta-protein of Alzheimer10/19/05’s disease. Am J Pathol 136 255–260 Occurrence Handle2407121

    PubMed  Google Scholar 

  • S Al-Sarraj T Hortobagyi S Wise (2004) ArticleTitleβ-Amyloid precursor protein (βAPP) immunohistochemistry detects axonal injury in less than 60 minutes after human brain trauma. J Neurol Neurosurg Psychiatry 63 534

    Google Scholar 

  • SE Arnold BT Hyman J Flory AR Damasio GW Van Hoesen (1991) ArticleTitleThe topographical and neuroanatomical distribution of neurofibrillary tangles and neuritic plaques in the cerebral cortex of patients with Alzheimer’s disease. Cereb Cortex 1 103–116 Occurrence Handle1822725

    PubMed  Google Scholar 

  • BJ Bacskai ST Kajdasz RH Christie C Carter D Games P Seubert D Schenk BT Hyman (2001) ArticleTitleImaging of amyloid-beta deposits in brains of living mice permits direct observation of clearance of plaques with immunotherapy. Nat Med 7 369–372 Occurrence Handle10.1038/85525 Occurrence Handle11231639

    Article  PubMed  Google Scholar 

  • TA Bayer O Wirths K Majtenyi T Hartmann G Multhaup K Beyreuther C Czech (2001) ArticleTitleKey factors in Alzheimer’s disease: beta-amyloid precursor protein processing, metabolism and intraneuronal transport. Brain Pathol 11 1–11 Occurrence Handle11145195

    PubMed  Google Scholar 

  • JG Beeson ER Shelton HW Chan FH Gage (1994) ArticleTitleAge and damage induced changes in amyloid protein precursor immunohistochemistry in the rat brain. J Comp Neurol 342 69–77 Occurrence Handle10.1002/cne.903420108 Occurrence Handle8207128

    Article  PubMed  Google Scholar 

  • H Benveniste G Einstein KR Kim C Hulette GA Johnson (1999) ArticleTitleDetection of neuritic plaques in Alzheimer’s disease by magnetic resonance microscopy. Proc Natl Acad Sci USA 96 14079–14084 Occurrence Handle10.1073/pnas.96.24.14079 Occurrence Handle10570201

    Article  PubMed  Google Scholar 

  • I Blasko R Beer M Bigl J Apelt G Franz D Rudzki G Ransmayr A Kampfl R Schliebs (2004) ArticleTitleExperimental traumatic brain injury in rats stimulates the expression, production and activity of Alzheimer’s disease beta-secretase (BACE-1). J Neural Transm 111 523–536 Occurrence Handle10.1007/s00702-003-0095-6 Occurrence Handle15057522

    Article  PubMed  Google Scholar 

  • PC Blumbergs G Scott J Manavis H Wainwright DA Simpson AJ McLean (1994) ArticleTitleStaining of amyloid precursor protein to study axonal damage in mild head injury. Lancet 344 1055–1056 Occurrence Handle10.1016/S0140-6736(94)91712-4 Occurrence Handle7523810

    Article  PubMed  Google Scholar 

  • PC Blumbergs G Scott J Manavis H Wainwright DA Simpson AJ McLean (1995) ArticleTitleTopography of axonal injury as defined by amyloid precursor protein and the sector scoring method in mild and severe closed head injury. J Neurotrauma 12 565–572 Occurrence Handle8683607

    PubMed  Google Scholar 

  • H Braak E Braak (1991) ArticleTitleNeuropathological stageing of Alzheimer-related changes. Acta Neuropathol (Berl) 82 239–259 Occurrence Handle10.1007/BF00308809

    Article  Google Scholar 

  • HM Bramlett S Kraydieh EJ Green WD Dietrich (1997) ArticleTitleTemporal and regional patterns of axonal damage following traumatic brain injury: a beta-amyloid precursor protein immunocytochemical study in rats. J Neuropathol Exp Neurol 56 1132–1141 Occurrence Handle9329457

    PubMed  Google Scholar 

  • GA Broe AS Henderson H Creasey E McCusker AE Korten AF Jorm W Longley JC Anthony (1990) ArticleTitleA case-control study of Alzheimer’s disease in Australia. Neurology 40 1698–1707 Occurrence Handle2146525

    PubMed  Google Scholar 

  • J Bruns SuffixJr WA Hauser (2003) ArticleTitleThe epidemiology of traumatic brain injury: a review. Epilepsia 44 2–10 Occurrence Handle10.1046/j.1528-1157.44.s10.3.x

    Article  Google Scholar 

  • JD Buxbaum JL Christensen AA Ruefli P Greengard JF Loring (1993) ArticleTitleExpression of APP in brains of transgenic mice containing the entire human APP gene. Biochem Biophys Res Commun 197 639–645 Occurrence Handle10.1006/bbrc.1993.2527 Occurrence Handle8267600

    Article  PubMed  Google Scholar 

  • JD Buxbaum G Thinakaran V Koliatsos J O’Callahan HH Slunt DL Price SS Sisodia (1998) ArticleTitleAlzheimer amyloid protein precursor in the rat hippocampus: transport and processing through the perforant path. J Neurosci 18 9629–9637 Occurrence Handle9822724

    PubMed  Google Scholar 

  • V Chandra E Kokmen BS Schoenberg CM Beard (1989) ArticleTitleHead trauma with loss of consciousness as a risk factor for Alzheimer’s disease. Neurology 39 1576–1578 Occurrence Handle2586772

    PubMed  Google Scholar 

  • XH Chen R Siman A Iwata DF Meaney JQ Trojanowski DH Smith (2004) ArticleTitleLong-term accumulation of amyloid-{beta}, {beta}-secretase, presenilin-1, and caspase-3 in damaged axons following brain trauma. Am J Pathol 165 357–371 Occurrence Handle15277212

    PubMed  Google Scholar 

  • JR Ciallella MD Ikonomovic WR Paljug YI Wilbur CE Dixon PM Kochanek DW Marion ST DeKosky (2002) ArticleTitleChanges in expression of amyloid precursor protein and interleukin-1beta after experimental traumatic brain injury in rats. J Neurotrauma 19 1555–1567 Occurrence Handle10.1089/089771502762300229 Occurrence Handle12542857

    Article  PubMed  Google Scholar 

  • J Clinton MW Ambler GW Roberts (1991) ArticleTitlePost-traumatic Alzheimer’s disease: preponderance of a single plaque type. Neuropathol Appl Neurobiol 17 69–74 Occurrence Handle2057052

    PubMed  Google Scholar 

  • R Cornish PC Blumbergs J Manavis G Scott NR Jones PL Reilly (2000) ArticleTitleTopography and severity of axonal injury in human spinal cord trauma using amyloid precursor protein as a marker of axonal injury. Spine 25 1227–1233 Occurrence Handle10.1097/00007632-200005150-00005 Occurrence Handle10806498

    Article  PubMed  Google Scholar 

  • MR Emmerling MC Morganti-Kossmann T Kossmann PF Stahel MD Watson LM Evans PD Mehta K Spiegel YM Kuo AE Roher CA Raby (2000) ArticleTitleTraumatic brain injury elevates the Alzheimer’s amyloid peptide A beta 42 in human CSF. A possible role for nerve cell injury. Ann NY Acad Sci 903 118–122 Occurrence Handle10818496

    PubMed  Google Scholar 

  • S Fleminger DL Oliver S Lovestone S Rabe-Hesketh A Giora (2003) ArticleTitleHead injury as a risk factor for Alzheimer’s disease: the evidence 10 years on; a partial replication. J Neurol Neurosurg Psychiatry 74 857–862 Occurrence Handle10.1136/jnnp.74.7.857 Occurrence Handle12810767

    Article  PubMed  Google Scholar 

  • G Franz R Beer A Kampfl K Engelhardt E Schmutzhard H Ulmer F Deisenhammer (2003) ArticleTitleAmyloid beta 1–42 and tau in cerebrospinal fluid after severe traumatic brain injury. Neurology 60 1457–1461 Occurrence Handle12743231

    PubMed  Google Scholar 

  • PE Gallant (1992) ArticleTitleThe direct effects of graded axonal compression on axoplasm and fast axoplasmic transport. J Neuropathol Exp Neurol 51 220–230 Occurrence Handle1371545

    PubMed  Google Scholar 

  • JF Geddes GH Vowles TW Beer DW Ellison (1997) ArticleTitleThe diagnosis of diffuse axonal injury: implications for forensic practice. Neuropathol Appl Neurobiol 23 339–347 Occurrence Handle10.1046/j.1365-2990.1997.4498044.x Occurrence Handle9292874

    Article  PubMed  Google Scholar 

  • JF Geddes GH Vowles JA Nicoll T Revesz (1999) ArticleTitleNeuronal cytoskeletal changes are an early consequence of repetitive head injury. Acta Neuropathol (Berl) 98 171–178 Occurrence Handle10.1007/s004010051066

    Article  Google Scholar 

  • JF Geddes GH Vowles SF Robinson JC Sutcliffe (1996) ArticleTitleNeurofibrillary tangles, but not Alzheimer-type pathology, in a young boxer. Neuropathol Appl Neurobiol 22 12–16 Occurrence Handle10.1046/j.1365-2990.1996.2598025.x Occurrence Handle8866777

    Article  PubMed  Google Scholar 

  • JF Geddes HL Whitwell DI Graham (2000) ArticleTitleTraumatic axonal injury: practical issues for diagnosis in medicolegal cases. Neuropathol Appl Neurobiol 26 105–116 Occurrence Handle10.1046/j.1365-2990.2000.026002105.x Occurrence Handle10840273

    Article  PubMed  Google Scholar 

  • L Genis Y Chen E Shohami DM Michaelson (2000) ArticleTitleTau hyperphosphorylation in apolipoprotein E-deficient and control mice after closed head injury. J Neurosci Res 60 559–564 Occurrence Handle10.1002/(SICI)1097-4547(20000515)60:4<559::AID-JNR15>3.0.CO;2-K Occurrence Handle10797559

    Article  PubMed  Google Scholar 

  • TA Gennarelli R Tipperman WL Maxwell DI Graham JH Adams A Irvine (1993) ArticleTitleTraumatic damage to the nodal axolemma: an early, secondary injury. Acta Neurochir (Wien) (Suppl) 57 49–52

    Google Scholar 

  • SM Gentleman DI Graham GW Roberts (1993a) ArticleTitleMolecular pathology of head trauma: altered beta APP metabolism and the aetiology of Alzheimer’s disease. Prog Brain Res 96 237–246

    Google Scholar 

  • SM Gentleman MJ Nash CJ Sweeting DI Graham GW Roberts (1993b) ArticleTitleBeta-amyloid precursor protein (beta APP) as a marker for axonal injury after head injury. Neurosci Lett 160 139–144 Occurrence Handle10.1016/0304-3940(93)90398-5

    Article  Google Scholar 

  • SM Gentleman PD Leclercq L Moyes DI Graham C Smith WS Griffin JA Nicoll (2004) ArticleTitleLong-term intracerebral inflammatory response after traumatic brain injury. Forensic Sci Int 146 97–104 Occurrence Handle10.1016/j.forsciint.2004.06.027 Occurrence Handle15542269

    Article  PubMed  Google Scholar 

  • SM Gentleman GW Roberts TA Gennarelli WL Maxwell JH Adams S Kerr DI Graham (1995) ArticleTitleAxonal injury: a universal consequence of fatal closed head injury? Acta Neuropathol (Berl) 89 537–543

    Google Scholar 

  • S Gottlieb (2000) ArticleTitleHead injury doubles the risk for Alzheimer’s disease. Br Med J 321 1100

    Google Scholar 

  • DI Graham SM Gentleman JA Nicoll MC Royston JE McKenzie GW Roberts WS Griffin (1996) ArticleTitleAltered beta-APP metabolism after head injury and its relationship to the aetiology of Alzheimer’s disease. Acta Neurochir (Wien) (Suppl) 66 96–102

    Google Scholar 

  • WS Griffin JG Sheng SM Gentleman DI Graham RE Mrak GW Roberts (1994) ArticleTitleMicroglial interleukin-1 alpha expression in human head injury: correlations with neuronal and neuritic beta-amyloid precursor protein expression. Neurosci Lett 176 133–136 Occurrence Handle10.1016/0304-3940(94)90066-3 Occurrence Handle7830934

    Article  PubMed  Google Scholar 

  • A Hamberger YL Huang H Zhu F Bao M Ding K Blennow A Olsson HA Hansson D Viano KG Haglid (2003) ArticleTitleRedistribution of neurofilaments and accumulation of beta-amyloid protein after brain injury by rotational acceleration of the head. J Neurotrauma 20 169–178 Occurrence Handle10.1089/08977150360547080 Occurrence Handle12675970

    Article  PubMed  Google Scholar 

  • JA Hardy GA Higgins (1992) ArticleTitleAlzheimer’s disease: the amyloid cascade hypothesis. Science 256 184–185 Occurrence Handle1566067

    PubMed  Google Scholar 

  • RE Hartman H Laurer L Longhi KR Bales SM Paul TK McIntosh DM Holtzman (2002) ArticleTitleApolipoprotein E4 influences amyloid deposition but not cell loss after traumatic brain injury in a mouse model of Alzheimer’s disease. J Neurosci 22 10083–10087 Occurrence Handle12451108

    PubMed  Google Scholar 

  • C Heurteaux V Bertaina C Widmann M Lazdunski (1993) ArticleTitleK+ 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 USA 90 9431–9435 Occurrence Handle8415718

    PubMed  Google Scholar 

  • S Hoshino S Kobayashi T Furukawa T Asakura A Teramoto (2003) ArticleTitleMultiple immunostaining methods to detect traumatic axonal injury in the rat fluid-percussion brain injury model. Neurol Med Chir (Tokyo) 43 165–173 Occurrence Handle10.2176/nmc.43.165

    Article  Google Scholar 

  • S Hoshino A Tamaoka M Takahashi S Kobayashi T Furukawa Y Oaki O Mori S Matsuno S Shoji M Inomata A Teramoto (1998) ArticleTitleEmergence of immunoreactivities for phosphorylated tau and amyloid-beta protein in chronic stage of fluid percussion injury in rat brain. Neuroreport 9 1879–1883 Occurrence Handle9665619

    PubMed  Google Scholar 

  • A Huber K Gabbert J Keleman J Cervos-Navarro (1990) ArticleTitleDensity of amyloid plaques in brain after head trauma. J Neurotrauma (Suppl 1) S180

    Google Scholar 

  • M Iino M Nakatome Y Ogura H Fujimura H Kuroki H Inoue Y Ino T Fujii T Terao R Matoba (2003) ArticleTitleReal-time PCR quantitation of FE65 a beta-amyloid precursor protein-binding protein after traumatic brain injury in rats. Int J Legal Med 117 153–159 Occurrence Handle12707777

    PubMed  Google Scholar 

  • MD Ikonomovic K Uryu EE Abrahamson JR Ciallella JQ Trojanowski VM Lee RS Clark DW Marion SR Wisniewski ST DeKosky (2004) ArticleTitleAlzheimer’s pathology in human temporal cortex surgically excised after severe brain injury. Exp Neurol 190 192–203 Occurrence Handle10.1016/j.expneurol.2004.06.011 Occurrence Handle15473992

    Article  PubMed  Google Scholar 

  • EA Irving DL Bentley AA Parsons (2001) ArticleTitleAssessment of white matter injury following prolonged focal cerebral ischaemia in the rat. Acta Neuropathol (Berl) 102 627–635

    Google Scholar 

  • EA Irving J Nicoll DI Graham D Dewar (1996) ArticleTitleIncreased tau immunoreactivity in oligodendrocytes following human stroke and head injury. Neurosci Lett 213 189–192 Occurrence Handle8873146

    PubMed  Google Scholar 

  • A Iwata XH Chen TK McIntosh KD Browne D Smith (2002) ArticleTitleLong-term accumulation of amyloid-beta in axons following brain trauma without persistent upregulation of amyloid precursor protein genes. J Neuropathol Exp Neurol 61 1056–1068 Occurrence Handle12484568

    PubMed  Google Scholar 

  • KA Jellinger (2004) ArticleTitleTraumatic brain injury as a risk factor for Alzheimer’s disease. J Neurol Neurosurg Psychiatry 75 511–512

    Google Scholar 

  • RN Kalaria SU Bhatti WD Lust G Perry (1993) ArticleTitleThe amyloid precursor protein in ischemic brain injury and chronic hypoperfusion. Ann NY Acad Sci 695 190–193 Occurrence Handle8239281

    PubMed  Google Scholar 

  • T Kawarabayashi M Shoji Y Harigaya H Yamaguchi S Hirai (1991) ArticleTitleExpression of APP in the early stage of brain damage. Brain Res 563 334–338 Occurrence Handle10.1016/0006-8993(91)91558-I Occurrence Handle1786548

    Article  PubMed  Google Scholar 

  • HS Kim SH Lee SS Kim YK Kim SJ Jeong J Ma DH Han BK Cho YH Suh (1998) ArticleTitlePost-ischemic changes in the expression of Alzheimer’s APP isoforms in rat cerebral cortex. Neuroreport 9 533–537 Occurrence Handle9512402

    PubMed  Google Scholar 

  • J Koistinaho I Pyykonen R Keinanen T Hokfelt (1996) ArticleTitleExpression of beta-amyloid precursor protein mRNAs following transient focal ischaemia. Neuroreport 7 2727–2731 Occurrence Handle8981456

    PubMed  Google Scholar 

  • EH Koo SS Sisodia DR Archer LJ Martin A Weidemann K Beyreuther P Fischer CL Masters DL Price (1990) ArticleTitlePrecursor of amyloid protein in Alzheimer disease undergoes fast anterograde axonal transport. Proc Natl Acad Sci USA 87 1561–1565 Occurrence Handle1689489

    PubMed  Google Scholar 

  • MP Kung ZP Zhuang C Hou HF Kung (2004) ArticleTitleDevelopment and evaluation of iodinated tracers targeting amyloid plaques for SPECT imaging. J Mol Neurosci 24 49–54 Occurrence Handle10.1385/JMN:24:1:049 Occurrence Handle15314249

    Article  PubMed  Google Scholar 

  • M Lambri V Djurovic M Kibble N Cairns S Al-Sarraj (2001) ArticleTitleSpecificity and sensitivity of betaAPP in head injury. Clin Neuropathol 20 263–271 Occurrence Handle11758782

    PubMed  Google Scholar 

  • HL Laurer FM Bareyre VM Lee JQ Trojanowski L Longhi R Hoover KE Saatman R Raghupathi S Hoshino MS Grady TK McIntosh (2001) ArticleTitleMild head injury increasing the brain’s vulnerability to a second concussive impact. J Neurosurg 95 859–870 Occurrence Handle11702878

    PubMed  Google Scholar 

  • SP Lee MF Falangola RA Nixon K Duff JA Helpern (2004) ArticleTitleVisualization of beta-amyloid plaques in a transgenic mouse model of Alzheimer’s disease using MR microscopy without contrast reagents. Magn Reson Med 52 538–544 Occurrence Handle10.1002/mrm.20196 Occurrence Handle15334572

    Article  PubMed  Google Scholar 

  • A Lewen GL Li P Nilsson Y Olsson L Hillered (1995) ArticleTitleTraumatic brain injury in rat produces changes of beta-amyloid precursor protein immunoreactivity. Neuroreport 6 357–360 Occurrence Handle7756628

    PubMed  Google Scholar 

  • A Lewen GL Li Y Olsson L Hillered (1996) ArticleTitleChanges in microtubule-associated protein 2 and amyloid precursor protein immunoreactivity following traumatic brain injury in rat: influence of MK-801 treatment. Brain Res 719 161–171 Occurrence Handle10.1016/0006-8993(96)00081-9 Occurrence Handle8782876

    Article  PubMed  Google Scholar 

  • L Lin CJ LeBlanc TW Deacon O Isacson (1998) ArticleTitleChronic cognitive deficits and amyloid precursor protein elevation after selective immunotoxin lesions of the basal forebrain cholinergic system. Neuroreport 9 547–552 Occurrence Handle9512404

    PubMed  Google Scholar 

  • TC Lye EA Shores (2000) ArticleTitleTraumatic brain injury as a risk factor for Alzheimer’s disease: a review. Neuropsychol Rev 10 115–129 Occurrence Handle10.1023/A:1009068804787 Occurrence Handle10937919

    Article  PubMed  Google Scholar 

  • DP Macfarlane JA Nicoll C Smith DI Graham (1999) ArticleTitleAPOE epsilon4 allele and amyloid beta-protein deposition in long term survivors of head injury. Neuroreport 10 3945–3948 Occurrence Handle10716238

    PubMed  Google Scholar 

  • M Masumura R Hata H Uramoto N Murayama T Ohno T Sawada (2000) ArticleTitleAltered expression of amyloid precursors proteins after traumatic brain injury in rats: in situ hybridization and immunohistochemical study. J Neurotrauma 17 123–134 Occurrence Handle10709870

    PubMed  Google Scholar 

  • WL Maxwell BJ McCreath DI Graham TA Gennarelli (1995) ArticleTitleCytochemical 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 Neurocytol 24 925–942 Occurrence Handle10.1007/BF01215643 Occurrence Handle8719820

    Article  PubMed  Google Scholar 

  • WL Maxwell JT Povlishock DL Graham (1997) ArticleTitleA mechanistic analysis of nondisruptive axonal injury: a review. J Neurotrauma 14 419–440 Occurrence Handle9257661

    PubMed  Google Scholar 

  • WL Maxwell C Watt DI Graham TA Gennarelli (1993) ArticleTitleUltrastructural evidence of axonal shearing as a result of lateral acceleration of the head in non-human primates. Acta Neuropathol (Berl) 86 136–144 Occurrence Handle10.1007/BF00334880

    Article  Google Scholar 

  • JE McKenzie SM Gentleman GW Roberts DI Graham MC Royston (1994) ArticleTitleIncreased numbers of beta APP-immunoreactive neurones in the entorhinal cortex after head injury. Neuroreport 6 161–164 Occurrence Handle7703405

    PubMed  Google Scholar 

  • KJ McKenzie DR McLellan SM Gentleman WL Maxwell TA Gennarelli DI Graham (1996) ArticleTitleIs beta-APP a marker of axonal damage in short-surviving head injury? Acta Neuropathol (Berl) 92 608–613 Occurrence Handle10.1007/s004010050568

    Article  Google Scholar 

  • KM Mehta A Ott S Kalmijn AJ Slooter CM van Duijn A Hofman MM Breteler (1999) ArticleTitleHead trauma and risk of dementia and Alzheimer’s disease: The Rotterdam Study. Neurology 53 1959–1962 Occurrence Handle10599765

    PubMed  Google Scholar 

  • PJ Morin CR Abraham A Amaratunga RJ Johnson G Huber JH Sandell RE Fine (1993) ArticleTitleAmyloid precursor protein is synthesized by retinal ganglion cells, rapidly transported to the optic nerve plasma membrane and nerve terminals, and metabolized. J Neurochem 61 464–473 Occurrence Handle7687653

    PubMed  Google Scholar 

  • H Murai JE Pierce R Raghupathi DH Smith KE Saatman JQ Trojanowski VM Lee JF Loring C Eckman S Younkin TK McIntosh (1998) ArticleTitleTwofold 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 Neurol 392 428–438 Occurrence Handle10.1002/(SICI)1096-9861(19980323)392:4<428::AID-CNE2>3.0.CO;2-2 Occurrence Handle9514508

    Article  PubMed  Google Scholar 

  • N Murakami T Yamaki Y Iwamoto T Sakakibara N Kobori S Fushiki S Ueda (1998) ArticleTitleExperimental brain injury induces expression of amyloid precursor protein, which may be related to neuronal loss in the hippocampus. J Neurotrauma 15 993–1003 Occurrence Handle9840772

    PubMed  Google Scholar 

  • Y Nakagawa M Nakamura TK McIntosh A Rodriguez JA Berlin DH Smith KE Saatman R Raghupathi J Clemens TC Saido ML Schmidt VM Lee JQ Trojanowski (1999) ArticleTitleTraumatic brain injury in young, amyloid-beta peptide overexpressing transgenic mice induces marked ipsilateral hippocampal atrophy and diminished Abeta deposition during aging. J Comp Neurol 411 390–398 Occurrence Handle10.1002/(SICI)1096-9861(19990830)411:3<390::AID-CNE3>3.0.CO;2-# Occurrence Handle10413774

    Article  PubMed  Google Scholar 

  • Y Nakagawa L Reed M Nakamura TK McIntosh DH Smith KE Saatman R Raghupathi J Clemens TC Saido VM Lee JQ Trojanowski (2000) ArticleTitleBrain trauma in aged transgenic mice induces regression of established abeta deposits. Exp Neurol 163 244–252 Occurrence Handle10.1006/exnr.2000.7375 Occurrence Handle10785464

    Article  PubMed  Google Scholar 

  • C Niess U Grauel SW Toennes H Bratzke (2002) ArticleTitleIncidence of axonal injury in human brain tissue. Acta Neuropathol (Berl) 104 79–84 Occurrence Handle10.1007/s00401-002-0525-9

    Article  Google Scholar 

  • J Nunan DH Small (2000) ArticleTitleRegulation of APP cleavage by alpha-, beta- and gamma-secretases. FEBS Lett 483 6–10 Occurrence Handle10.1016/S0014-5793(00)02076-7 Occurrence Handle11033346

    Article  PubMed  Google Scholar 

  • T Ohgami T Kitamoto J Tateishi (1992) ArticleTitleAlzheimer’s amyloid precursor protein accumulates within axonal swellings in human brain lesions. Neurosci Lett 136 75–78 Occurrence Handle10.1016/0304-3940(92)90651-M Occurrence Handle1635670

    Article  PubMed  Google Scholar 

  • A Olsson L Csajbok M Ost K Hoglund K Nylen L Rosengren B Nellgard K Blennow (2004) ArticleTitleMarked increase of beta-amyloid ((1–42)) and amyloid precursor protein in ventricular cerebrospinal fluid after severe traumatic brain injury. J Neurol 251 870–876 Occurrence Handle10.1007/s00415-004-0451-y Occurrence Handle15258792

    Article  PubMed  Google Scholar 

  • N Otsuka M Tomonaga K Ikeda (1991) ArticleTitleRapid appearance of beta-amyloid precursor protein immunoreactivity in damaged axons and reactive glial cells in rat brain following needle stab injury. Brain Res 568 335–338 Occurrence Handle10.1016/0006-8993(91)91422-W Occurrence Handle1814579

    Article  PubMed  Google Scholar 

  • G Palacios JM Palacios G Mengod P Frey (1992) ArticleTitleBeta-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 Res 15 195–206 Occurrence Handle10.1016/0169-328X(92)90109-O Occurrence Handle1331676

    Article  PubMed  Google Scholar 

  • EH Pettus CW Christman ML Giebel JT Povlishock (1994) ArticleTitleTraumatically induced altered membrane permeability: its relationship to traumatically induced reactive axonal change. J Neurotrauma 11 507–522 Occurrence Handle7861444

    PubMed  Google Scholar 

  • EH Pettus JT Povlishock (1996) ArticleTitleCharacterization of a distinct set of intra-axonal ultrastructural changes associated with traumatically induced alteration in axolemmal permeability. Brain Res 722 1–11 Occurrence Handle10.1016/0006-8993(96)00113-8 Occurrence Handle8813344

    Article  PubMed  Google Scholar 

  • JE Pierce JQ Trojanowski DI Graham DH Smith TK McIntosh (1996) ArticleTitleImmunohistochemical characterization of alterations in the distribution of amyloid precursor proteins and beta-amyloid peptide after experimental brain injury in the rat. J Neurosci 16 1083–1090 Occurrence Handle8558237

    PubMed  Google Scholar 

  • BL Plassman RJ Havlik DC Steffens MJ Helms TN Newman D Drosdick C Phillips BA Gau KA Welsh-Bohmer JR Burke JM Guralnik JC Breitner (2000) ArticleTitleDocumented head injury in early adulthood and risk of Alzheimer’s disease and other dementias. Neurology 55 1158–1166 Occurrence Handle11071494

    PubMed  Google Scholar 

  • R Pluta E Kida AS Lossinsky AA Golabek MJ Mossakowski HM Wisniewski (1994) ArticleTitleComplete 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 Res 649 323–328 Occurrence Handle10.1016/0006-8993(94)91081-2 Occurrence Handle7525011

    Article  PubMed  Google Scholar 

  • JT Povlishock (1993) ArticleTitlePathobiology of traumatically induced axonal injury in animals and man. Ann Emerg Med 22 980–986 Occurrence Handle10.1016/S0196-0644(05)82738-6 Occurrence Handle8503536

    Article  PubMed  Google Scholar 

  • JT Povlishock A Marmarou T McIntosh JQ Trojanowski J Moroi (1997) ArticleTitleImpact acceleration injury in the rat: evidence for focal axolemmal change and related neurofilament sidearm alteration. J Neuropathol Exp Neurol 56 347–359 Occurrence Handle9100665

    PubMed  Google Scholar 

  • RR Reichard CL White Suffix3rd CL Hladik D Dolinak (2003) ArticleTitleBeta-amyloid precursor protein staining of nonaccidental central nervous system injury in pediatric autopsies. J Neurotrauma 20 347–355 Occurrence Handle10.1089/089771503765172309 Occurrence Handle12866814

    Article  PubMed  Google Scholar 

  • RR Reichard CL White Suffix3rd RN Hogan CL Hladik D Dolinak (2004) ArticleTitleBeta-amyloid precursor protein immunohistochemistry in the evaluation of pediatric traumatic optic nerve injury. Ophthalmology 111 822–827 Occurrence Handle10.1016/j.ophtha.2003.07.016 Occurrence Handle15051219

    Article  PubMed  Google Scholar 

  • GW Roberts D Allsop C Bruton (1990) ArticleTitleThe occult aftermath of boxing. J Neurol Neurosurg Psychiatry 53 373–378 Occurrence Handle2191084

    PubMed  Google Scholar 

  • GW Roberts SM Gentleman A Lynch DI Graham (1991) ArticleTitlebeta A4 amyloid protein deposition in brain after head trauma. Lancet 338 1422–1423 Occurrence Handle10.1016/0140-6736(91)92724-G Occurrence Handle1683421

    Article  PubMed  Google Scholar 

  • GW Roberts SM Gentleman A Lynch L Murray M Landon DI Graham (1994) ArticleTitleBeta amyloid protein deposition in the brain after severe head injury: implications for the pathogenesis of Alzheimer’s disease. J Neurol Neurosurg Psychiatry 57 419–425 Occurrence Handle8163989

    PubMed  Google Scholar 

  • DE Schmechel D Goldgaber DS Burkhart JR Gilbert DC Gajdusek AD Roses (1988) ArticleTitleCellular localization of messenger RNA encoding amyloid-beta-protein in normal tissue and in Alzheimer disease. Alzheimer Dis Assoc Disord 2 96–111 Occurrence Handle3063300

    PubMed  Google Scholar 

  • ML Schmidt V Zhukareva KL Newell VM Lee JQ Trojanowski (2001) ArticleTitleTau isoform profile and phosphorylation state in dementia pugilistica recapitulate Alzheimer’s disease. Acta Neuropathol (Berl) 101 518–524

    Google Scholar 

  • C Schmitz BP Rutten A Pielen S Schafer O Wirths G Tremp C Czech V Blanchard G Multhaup P Rezaie H Korr HW Steinbusch L Pradier TA Bayer (2004) ArticleTitleHippocampal neuron loss exceeds amyloid plaque load in a transgenic mouse model of Alzheimer’s disease. Am J Pathol 164 1495–1502 Occurrence Handle15039236

    PubMed  Google Scholar 

  • JN Scott IM Parhad AW Clark (1991) ArticleTitleBeta-amyloid precursor protein gene is differentially expressed in axotomized sensory and motor systems. Brain Res Mol Brain Res 10 315–325 Occurrence Handle10.1016/0169-328X(91)90090-K Occurrence Handle1656158

    Article  PubMed  Google Scholar 

  • DJ Selkoe (2001) ArticleTitleAlzheimer’s disease: genes proteins, and therapy. Physiol Rev 81 741–766 Occurrence Handle11274343

    PubMed  Google Scholar 

  • P Seubert T Oltersdorf MG Lee R Barbour C Blomquist DL Davis K Btyany LC Fritz D Glasko LJ Thal I Lieberburg DB Schenk (1993) ArticleTitleSecretion of beta-amyloid precursor protein cleaved at the amino-terminus of the beta-amyloid peptide. Nature 361 260–263 Occurrence Handle10.1038/361260a0 Occurrence Handle7678698

    Article  PubMed  Google Scholar 

  • FE Sherriff LR Bridges SM Gentleman S Sivaloganathan S Wilson (1994) ArticleTitleMarkers of axonal injury in post mortem human brain. Acta Neuropathol (Berl) 88 433–439

    Google Scholar 

  • FE Sherriff LR Bridges S Sivaloganathan (1994) ArticleTitleEarly detection of axonal injury after human head trauma using immunocytochemistry for beta-amyloid precursor protein. Acta Neuropathol (Berl) 87 55–62

    Google Scholar 

  • K Shigematsu PL McGeer (1992) ArticleTitleAccumulation of amyloid precursor protein in neurons after intraventricular injection of colchicine. Am J Pathol 140 787–794 Occurrence Handle1373270

    PubMed  Google Scholar 

  • K Shoghi-Jadid GW Small ED Agdeppa V Kepe LM Ercoli P Siddarth S Read N Satyamurthy A Petric SC Huang JR Barrio (2002) ArticleTitleLocalization of neurofibrillary tangles and beta-amyloid plaques in the brains of living patients with Alzheimer disease. Am J Geriatr Psychiatry 10 24–35 Occurrence Handle10.1176/appi.ajgp.10.1.24 Occurrence Handle11790632

    Article  PubMed  Google Scholar 

  • R Siman JP Card RB Nelson LG Davis (1989) ArticleTitleExpression of beta-amyloid precursor protein in reactive astrocytes following neuronal damage. Neuron 3 275–285 Occurrence Handle10.1016/0896-6273(89)90252-3 Occurrence Handle2518369

    Article  PubMed  Google Scholar 

  • SS Sisodia EH Koo PN Hoffman G Perry DL Price (1993) ArticleTitleIdentification and transport of full-length amyloid precursor proteins in rat peripheral nervous system. J Neurosci 13 3136–3142 Occurrence Handle8331390

    PubMed  Google Scholar 

  • C Smith DI Graham LS Murray JA Nicoll (2003) ArticleTitleTau immunohistochemistry in acute brain injury. Neuropathol Appl Neurobiol 29 496–502 Occurrence Handle10.1046/j.1365-2990.2003.00488.x Occurrence Handle14507341

    Article  PubMed  Google Scholar 

  • DH Smith XH Chen A Iwata DI Graham (2003) ArticleTitleAmyloid beta accumulation in axons after traumatic brain injury in humans. J Neurosurg 98 1072–1077 Occurrence Handle12744368

    PubMed  Google Scholar 

  • DH Smith XH Chen M Nonaka JQ Trojanowski VM Lee KE Saatman MJ Leoni BN Xu JA Wolf DF Meaney (1999) ArticleTitleAccumulation of amyloid beta and tau and the formation of neurofilament inclusions following diffuse brain injury in the pig. J Neuropathol Exp Neurol 58 982–992 Occurrence Handle10499440

    PubMed  Google Scholar 

  • DH Smith DF Meaney (2000) ArticleTitleAxonal damage in traumatic brain injury. Neuroscientist 6 483–495

    Google Scholar 

  • DH Smith M Nakamura TK McIntosh J Wang A Rodriguez XH Chen R Raghupathi KE Saatman J Clemens ML Schmidt VM Lee JQ Trojanowski (1998) ArticleTitleBrain trauma induces massive hippocampal neuron death linked to a surge in beta-amyloid levels in mice overexpressing mutant amyloid precursor protein. Am J Pathol 153 1005–1010 Occurrence Handle9736050

    PubMed  Google Scholar 

  • DT Stephenson K Rash JA Clemens (1992) ArticleTitleAmyloid precursor protein accumulates in regions of neurodegeneration following focal cerebral ischemia in the rat. Brain Res 593 128–135 Occurrence Handle10.1016/0006-8993(92)91274-I Occurrence Handle1458315

    Article  PubMed  Google Scholar 

  • JR Stone SA Walker JT Povlishock (1999) ArticleTitleThe visualization of a new class of traumatically injured axons through the use of a modified method of microwave antigen retrieval. Acta Neuropathol (Berl) 97 335–345 Occurrence Handle10.1007/s004010050996

    Article  Google Scholar 

  • T Tokuda S Ikeda N Yanagisawa Y Ihara GG Glenner (1991) ArticleTitleRe-examination of ex-boxers’ brains using immunohistochemistry with antibodies to amyloid beta-protein and tau protein. Acta Neuropathol (Berl) 82 280–285 Occurrence Handle10.1007/BF00308813

    Article  Google Scholar 

  • PR Turner K O’Connor WP Tate WC Abraham (2003) ArticleTitleRoles of amyloid precursor protein and its fragments in regulating neural activity, plasticity and memory. Prog Neurobiol 70 1–32 Occurrence Handle10.1016/S0301-0082(03)00089-3 Occurrence Handle12927332

    Article  PubMed  Google Scholar 

  • K Uryu H Laurer T McIntosh D Pratico D Martinez S Leight VM Lee JQ Trojanowski (2002) ArticleTitleRepetitive mild brain trauma accelerates Abeta deposition, lipid peroxidation, and cognitive impairment in a transgenic mouse model of Alzheimer amyloidosis. J Neurosci 22 446–454 Occurrence Handle11784789

    PubMed  Google Scholar 

  • C Van Den Heuvel P Blumbergs J Finnie J Manavis S Lewis N Jones P Reilly R Pereira (2000) ArticleTitleUpregulation of amyloid precursor protein and its mRNA in an experimental model of paediatric head injury. J Clin Neurosci 7 140–145 Occurrence Handle10.1054/jocn.1999.0168 Occurrence Handle10844801

    Article  PubMed  Google Scholar 

  • C Van Den Heuvel PC Blumbergs JW Finnie J Manavis NR Jones PL Reilly RA Pereira (1999) ArticleTitleUpregulation of amyloid precursor protein messenger RNA in response to traumatic brain injury: an ovine head impact model. Exp Neurol 159 441–450 Occurrence Handle10.1006/exnr.1999.7150 Occurrence Handle10506515

    Article  PubMed  Google Scholar 

  • C Van Den Heuvel S Lewis M Wong J Manavis J Finnie P Blumbergs N Jones P Reilly (1998) ArticleTitleDiffuse neuronal perikaryon amyloid precursor protein immunoreactivity in a focal head impact model. Acta Neurochir (Wien) (Suppl) 71 209–211

    Google Scholar 

  • WC Wallace V Bragin NK Robakis K Sambamurti D VanderPutten CR Merril KL Davis AC Santucci V Haroutunian (1991) ArticleTitleIncreased biosynthesis of Alzheimer amyloid precursor protein in the cerebral cortex of rats with lesions of the nucleus basalis of Meynert. Brain Res Mol Brain Res 10 173–178 Occurrence Handle10.1016/0169-328X(91)90108-A Occurrence Handle1649369

    Article  PubMed  Google Scholar 

  • AE Wilkinson LR Bridges S Sivaloganathan (1999) ArticleTitleCorrelation of survival time with size of axonal swellings in diffuse axonal injury. Acta Neuropathol (Berl) 98 197–202 Occurrence Handle10.1007/s004010051069

    Article  Google Scholar 

  • O Wirths G Multhaup TA Bayer (2004) ArticleTitleA modified beta-amyloid hypothesis: intraneuronal accumulation of the beta-amyloid peptide – the first step of a fatal cascade. J Neurochem 91 513–520 Occurrence Handle10.1111/j.1471-4159.2004.02737.x Occurrence Handle15485483

    Article  PubMed  Google Scholar 

  • PS Yam T Takasago D Dewar DI Graham J McCulloch (1997) ArticleTitleAmyloid precursor protein accumulates in white matter at the margin of a focal ischaemic lesion. Brain Res 760 150–157 Occurrence Handle10.1016/S0006-8993(97)00290-4 Occurrence Handle9237529

    Article  PubMed  Google Scholar 

  • FP Zemlan EC Jauch JJ Mulchahey SP Gabbita WS Rosenberg SG Speciale M Zuccarello (2002) ArticleTitleC-tau biomarker of neuronal damage in severe brain injured patients: association with elevated intracranial pressure and clinical outcome. Brain Res 947 131–139 Occurrence Handle10.1016/S0006-8993(02)02920-7 Occurrence Handle12144861

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Szczygielski, J., Mautes, A., Steudel, W. et al. Traumatic brain injury: cause or risk of Alzheimer’s disease? A review of experimental studies. J Neural Transm 112, 1547–1564 (2005). https://doi.org/10.1007/s00702-005-0326-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00702-005-0326-0

Navigation