Abstract
Traumatic brain injury (TBI) is one of the most devastating diseases in our society, accounting for a high percentage of mortality and disability. A major consequence of TBI is the rapid and long-term accumulation of proteins. This process largely reflects the interruption of axonal transport as a result of extensive axonal injury. Although many proteins are found accumulating after TBI, three have received particular attention; β-amyloid precursor protein and its proteolytic products, amyloid-β (Aβ) peptides, neurofilament proteins, and synuclein proteins. Massive coaccumulations of all of these proteins are found in damaged axons throughout the white matter after TBI. Additionally, these proteins form aggregates in other neuronal compartments and in brain parenchyma after brain trauma. Interestingly, TBI is also an epigenetic risk factor for developing neurodegenerative disorders, such as Alzheimer’s disease and Parkinson’s disease. Here, the similarities and differences of these accumulations with pathologies of neurodegenerative diseases will be explored. In addition, the potential deleterious roles of protein accumulations on functional outcome and progressive neurodegeneration following TBI will be examined.
Similar content being viewed by others
References
Adams J. H., Graham D. I., and Gennarelli T. A. (1991) Diffuse axonal injury in non-missile head injury. J. Neurol. Neurosurg. Psychiatry 54, 481–483.
Adams J. H., Doyle D., Ford I., et al. (1989) Diffuse axonal injury in head injury: definition, diagnosis, and grading. Histopathology 15, 49–59.
Adams J. H., Graham D. I., Murray L. S., and Scott G. (1982) Diffuse axonal injury due to nonmissile head injury in humans: an analysis of 45 cases. Ann. Neurol. 12, 557–563.
Arawaka S., Saito Y., Murayama S., and Mori H. (1998) Lewy body in neurodegeneration with brain iron accumulation type 1 is immunoreactive for alpha-synuclein. Neurology 51, 887–889.
Arima K., Ueda K., Sunohara N., et al. (1998) Immunoelectron-microscopic demonstration of NACP/alpha-synuclein-epitopes on the filamentous component of Lewy bodies in Parkinson’s disease and in dementia with Lewy bodies. Brain Res. 808, 93–100.
Auluck P. K., Chan H. Y., Trojanowski J. Q., Lee V. M., and Bonini N. M. (2002) Chaperone suppression of alpha-synuclein toxicity in a Drosophila model for Parkinson’s disease. Science 295, 865–868.
Baba M., Nakajo S., Tu P. H., et al. (1998) Aggregation of alpha-synuclein in Lewy bodies of sporadic Parkinson’s disease and dementia with Lewy bodies. Am. J. Pathol. 152, 879–884.
Ben Shlomo Y. (1997) The epidemiology of Parkinson’s disease. Baillieres Clin. Neurol. 6, 55–68.
Betarbet R., Sherer T. B., MacKenzie G., et al. (2000) Chronic systemic pesticide exposure reproduces features of Parkinson’s disease. Nat. Neurosci 3, 1301–1306.
Blumbergs P. C., Scott G., Manavis J., et al. (1995) Axonal injury in longterm survivors of traumatic head injury. J. Neurotrauma 12, 353.
Braak H., Del Tredici K., Rub U., et al. (2003) Staging of brain pathology related to sporadic Parkinson’s disease. Neurobiol. Aging 24, 197–211.
Braak H., Sandmann-Keil D., Gai W., and Braak E. (1999) Extensive axonal Lewy neurites in Parkinson’s disease: a novel pathological feature revealed by alpha-synuclein immunocytochemistry. Neurosci. Lett. 265, 67–69.
Bramlett H. M., Kraydieh S., Green E. J., and Dietrich W. D. (1997) Temporal 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.
Chen X.-H., Meaney D. F., Xu B.-N., et al. (1999) Evolution of neurofilament subtype accumulation in axons following diffuse brain injury in the pig. J. Neuropathol. Exp. Neurol. 58, 588–596.
Christman C. W., Grady M. S., Walker S. A., Holloway K. L., and Povlishock J. T. (1994) Ultrastructural studies of diffuse axonal injury in humans. J. Neurotrauma 11, 173–186.
Ciallella J. R., Ikonomovic M. D., Paljug W. R., et al. (2002) Changes in expression of amyloid precursor protein and interleukin-1beta after experimental traumatic brain injury in rats. J. Neurotrauma 19, 1555–1567.
Clark R. S.B., Chen M., Kochanek P. M., et al. (2001) Detection of single- and double-strand DNA breaks after traumatic brain injury in rats: comparison of in situ labeling techniques using DNA polymerase I, the Klenow fragment of DNA polymerase I, and terminal deoxynucleotidyl transferase. J. Neurotrauma 18, 675–689.
Conway K. A., Harper J. D., and Lansbury P. T. (1998) Accelerated in vitro fibril formation by a mutant alpha-synuclein linked to early-onset Parkinson disease. Nat. Med. 4, 1318–1320.
Cote F., Collard J. F., and Julien J.-P. (1993) Progressive neuronopathy in transgenic mice expressing the human neurofilament heavy gene: A mouse model of amyotrophic lateral sclerosis. Cell 73, 35–46.
De Strooper B., Saftig P., Craessaerts K., et al. (1998) Deficiency of presenilin-1 inhibits the normal cleavage of amyloid precursor protein. Nature 391, 387–390.
DeKosky S. T., Goss J. R., Miller P. D., et al. (1994) Upregulation of nerve growth factor following cortical trauma. Exp. Neurol. 130, 173–177.
Duda J. E., Giasson B. I., Mabon M. E., Lee V. M., and Trojanowski J. Q. (2002) Novel antibodies to synuclein show abundant striatal pathology in Lewy body diseases. Ann. Neurol. 52, 205–210.
Emmerling M. R., Morganti-Kossmann M. C., Kossmann T., et al. (2000) Traumatic brain injury elevates the Alzheimer’s amyloid peptide A beta 42 in human CSF. A possible role for nerve cell injury. Ann. N.Y. Acad. Sci. 903, 118–122.
Esler W. P. and Wolfe M. S. (2001) A portrait of Alzheimer secretases—new features and familiar faces. Science 293, 1449–1454.
Eyer J. and Peterson A. (1994) Neurofilament-deficient axon and perikaryal aggregates in viable transgenic mice expressing a neurofilament-beta-galactosidase fusion protein. Neuron 12, 389–405.
Factor S. A. and Weiner W. J. (1991) Prior history of head trauma in Parkinson’s disease. Mov. Disord. 6, 225–229.
Feany M. B. and Bender W. W. (2000) A Drosophila model of Parkinson’s disease. Nature 404, 394–398.
Franz G., Beer R., Kampfl A., et al. (2003) Amyloid beta 1–42 and tau in cerebrospinal fluid after severe traumatic brain injury. Neurology 60, 1457–1461.
Fujiwara H., Hasegawa M., Dohmae N., et al. (2002) alpha-Synuclein is phosphorylated in synucleinopathy lesions. Nat. Cell Biol. 4, 160–164.
Galvin J. E., Nakamura M., McIntosh T. K., et al. (2000) Neurofilament-rich intraneuronal inclusions exacerbate neurodegenerative sequelae of brain trauma in NFH/LacZ transgenic mice. Exp. Neurol. 165, 77–89.
Galvin J. E., Lee V. M. Y., Schmidt M. L., et al. (1999) Pathobiology of the Lewy body (LB); studies of purified LBS, monoclonal antibodies and LB-like inclusions in transgenic animal models. Adv. Neurol. 80, 313–324.
Galvan V., Chen S., Lu D., et al. (2002) Caspase cleavage of members of the amyloid precursor family of proteins. J. Neurochem. 82, 283–294.
Gennarelli T. A. (1993) Mechanisms of brain injury. J. Emerg. Med. 11(supp 1), 5–11.
Gentleman S. M., Nash M. J., Sweeting C. J., et al. (1993) β-amyloid precursor protein (β-APP) as a marker for axonal injury after head injury. Neurosci. Lett. 160, 134–144.
Giasson B. I., Duda J. E., Quinn S. M., et al. (2002) Neuronal alpha-synucleinopathy with severe movement disorder in mice expressing A53T human alpha-synuclein. Neuron 34, 521–533.
Giasson B. I., Duda J. E., Murray I. V., et al. (2000a) Oxidative damage linked to neurodegeneration by selective alpha-synuclein nitration in synucleinopathy lesions (comment). Science 290, 985–989.
Giasson B. I., Jakes R., Goedert M., et al. (2000b) A panel of epitope-specific antibodies detects protein domains distributed throughout human alpha-synuclein in Lewy bodies of Parkinson’s disease. J. Neurosci. Res. 59, 528–533.
Gorrie C., Oakes S., Duflou J., Blumbergs P., and Waite P. M. (2002) Axonal injury in children after motor vehicle crashes: extent, distribution, and size of axonal swellings using beta-APP immunohistochemistry. J. Neurotrauma 19, 1171–1182.
Gottlieb S. (2000) Head injury doubles the risk of Alzheimer’s disease. Br. Med. J. 321, 1100.
Grady M. S., McLaughlin M. R., Christman C. W., et al. (1993) The use of antibodies targeted against the neurofilament subunits for the detection of diffuse axonal injury in humans. J. Neuropathol. Exp. Neurol. 52, 143–152.
Graham D. I., Gentleman S. M., Lynch A., and Roberts G. W. (1995) Distribution of β-amyloid protein in the brain following severe head injury. Neuropath. Appl. Neurobiol. 21, 27–34.
Hamberger A., Huang Y. L., Zhu H., et al. (2003) Redistribution of neurofilaments and accumulation of beta-amyloid protein after brain injury by rotational acceleration of the head. J. Neurotrauma 20, 169–178.
Hartman R. E., Laurer H., Longhi L., et al. (2002) Apolipoprotein 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.
Higuchi M., Lee V. M., and Trojanowski J. Q. (2002) Tau and axonopathy in neurodegenerative disorders. Neuromol. Med. 2, 131–150.
Huh J. W., Laurer H. L., Raghupathi R., Helfaer M. A., and Saatman K. E. (2002) Rapid loss and partial recovery of neurofilament immunostaining following focal brain injury in mice. Exp. Neurol. 175, 198–208.
Hurtig H. I., Trojanowski J. Q., Galvin J., et al. (2000) Alpha-synuclein cortical Lewy bodies correlate with dementia in Parkinson’s disease. Neurology 54, 1916–1921.
Irizarry M. C., Growdon W., Gomez-Isla T., et al. (1998) Nigral and cortical Lewy bodies and dystrophic nigral neurites in Parkinson’s disease and cortical Lewy body disease contain alpha-synuclein immunoreactivity. J. Neuropathol. Exp. Neurol. 57, 334–337.
Iwata A., Chen X. H., McIntosh T. K., Browne K. D., and Smith D. H. (2002) Long-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.
Jellinger K. A., Paulus W., Wrocklage C., and Litvan I. (2001) Effects of closed traumatic brain injury and genetic factors on the development of Alzheimer’s disease. Eur. J. Neurol. 8, 707–710.
Julien J. P., Couillard-Despres S., and Meier J. (1998) Transgenic mice in the study of ALS: the role of neurofilaments. Brain Pathol. 8, 759–769.
Julien J. P. and Mushynski W. E. (1998) Neurofilaments in health and disease. Prog. Nucleic Acid Res. Mol. Biol. 61, 1–23.
Julien J. P. and Mushynski W. E. (1983) The distribution of phosphorylation sites among identified proteolytic fragments of mammalian neurofilaments. J. Biol. Chem. 258, 4019–4025.
Kamal A., Almenar-Queralt A., LeBlanc J. F., Roberts E. A., and Goldstein L. S. (2001) Kinesin-mediated axonal transport of a membrane compartment containing beta-secretase and presenilin-1 requires APP. Nature 414, 643–648.
Kamal A., Stokin G. B., Yang Z., Xia C. H., and Goldstein L. S. (2000) Axonal transport of amyloid precursor protein is mediated by direct binding to the kinesin light chain subunit of kinesin-I. Neuron 28, 449–459.
Kanayama G., Takeda M., Morihara T., et al. (1997) Temporal and regional profiles of cytoskeletal protein accumulation in the rat brain following traumatic brain injury. Psychiatry Clin. Neurosci. 51, 157–165.
Kruger R., Kuhn W., Muller T., et al. (1998) Ala30Pro mutation in the gene encoding alpha-synuclein in Parkinson’s disease. Nat. Genet. 18, 106–108.
Lambri M., Djurovic V., Kibble M., Cairns N., and Al Sarraj S. (2001) Specificity and sensitivity of betaAPP in head injury. Clin. Neuropathol. 20, 263–271.
Langston J. W., Ballard P., Tetrud J. W., and Irwin I. (1983) Chronic Parkinsonism in humans due to a product of meperidine-analog synthesis. Science 219, 979–980.
Laurer H. L., Bareyre F. M., Lee V. M.Y., et al. (2001) Mild head injury increases the brain’s vulnerability to a second concussive impact. J. Neurosurg. 95, 859–870.
Lees A. J. (1997) Trauma and Parkinson disease. Rev. Neurol. 153, 541–546.
Lewen A., Li G. L., Nilsson P., Olsson Y., and Hillered L. (1995) Traumatic brain injury in rat produces changes of β-amyloid precursor protein immunoreactivity. NeuroReport 6, 357–360.
Liu P. K., Robertson C. S., and Valadka A. (2002) The association between neuronal nitric oxide synthase and neuronal sensitivity in the brain after brain injury. Ann. N. Y. Acad. Sci. 962, 226–241.
Luth H. J., Holzer M., Gartner U., Staufenbiel M., and Arendt T. (2001) Expression of endothelial and inducible NOS-isoforms is increased in Alzheimer’s disease, in APP23 transgenic mice and after experimental brain lesion in rat: evidence for an induction by amyloid pathology. Brain Res. 913, 57–67.
Masliah E., Rockenstein E., Veinbergs I., et al. (2000) Dopaminergic loss and inclusion body formation in alpha-synuclein mice: implications for neurodegenerative disorders. Science 287, 1265–1269.
Maxwell W. L., Povlishock J. T., and Graham D.I. (1997) A mechanistic analysis of nondisruptive axonal injury: A review. J. Neurotrauma 14, 419–440.
McKenzie K. J., McLellan D. R., Gentleman S. M., et al. (1996) Is beta-APP a marker of axonal damage in short-surviving head injury? Acta Neuropathol. 92, 608–613.
Meaney D. F., Ross D. T., Winkelstein B. A., et al. (1994) Modification of the cortical impact model to produce axonal injury in the rat cerebral cortex. J. Neurotrauma 11, 599–612.
Mesenge C., Charriaut-Marlangue C., Verrecchia C., et al. (1998) Reduction of tyrosine nitration after N(omega)-nitro-L-arginine-methylester treatment of mice with traumatic brain injury. Eur. J. Pharmacol. 353, 53–57.
Morfini G., Pigino G., Beffert U., Busciglio J., and Brady S. T. (2002) Fast axonal transport misregulation and Alzheimer’s disease. Neuromol. Med. 2, 89–99.
Murai H., Pierce J. E.S., Raghupathi R., et al. (1998) Two-fold overexpression of human β-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.
Nakagawa Y., Reed L., Nakamura M., et al. (2000) Brain trauma in aged transgenic mice induces regression of established Aβ deposits. Exp. Neurol. 163, 244–252.
Nakagawa Y., Nakamura M., McIntosh T. K., et al. (1999) Traumatic brain injury in young amyloid-β peptide overexpressing transgenic mice induces marked ipsilateral hippocampal atrophy and dimininished Aβ deposition during aging. J. Comp. Neurol. 411, 390–398.
Nakamura M., Saatman K. E., Galvin J. E., et al. (1999) Increased vulnerability of NFH-LacZ transgenic mouse to traumatic brain injury-induced behavioral deficits and cell loss. J. Cereb. Blood Flow Metab. 19, 762–770.
Nayernouri T. (1985) Posttraumatic parkinsonism. Surg. Neurol. 24, 263–264.
Nemetz P. N., Leibson C., Naessens J. M., et al. (1999) Traumatic brain injury and time to onset of Alzheimer’s disease: a population-based study. Am. J. Epidemiol. 149, 32–40.
Newell K. L., Boyer P., Gomez-Tortosa E., et al. (1999) Alpha-synuclein immunoreactivity is present in axonal swellings in neuroaxonal dystrophy and acute traumatic brain injury. J. Neuropathol. Exp. Neurol. 58, 1263–1268.
Nixon R. A., Paskevich P. A., Sihag R. K., and Thayer C. Y. (1994) Phosphorylation on carboxyl terminus domains of neurofilament proteins in retinal ganglion cell neurons in vivo: influences on regional neurofilament accumulation, interneurofilament spacing, and axon caliber. J. Cell Biol. 126, 1031–1046.
Norris E. H., Giasson B. I., Ischiropoulos H., and Lee V. M.Y. (2003) Effects of oxidative and nitrative challenges on alpha-synuclein fibrillogenesis involve distinct mechanisms of protein modifications. J. Biol. Chem., 278, 27230–27240.
Nunan J. and Small D. H. (2000) Regulation of APP cleavage by alpha-, beta- and gamma-secretases. FEBS Lett. 483, 6–10.
Okonkwo D. O., Pettus E. H., Moroi J., and Povlishock J. T. (1998) Alteration of the neurofilament sidearm and its relation to neurofilament compaction occurring with traumatic axonal injury. Brain Res. 784, 1–6.
Paxinou E., Chen Q., Weisse M., et al. (2001) Induction of alpha-synuclein aggregation by intracellular nitrative insult. J. Neurosci. 21, 8053–8061.
Perrone C. C., Pernas-Alonso R., and di Porzio U. (2001) Neurofilament homeostasis and motoneurone degeneration. BioEssays 23, 24–33.
Pettus E. H. and Povlishock J. T. (1996) Characterization of a distinct set of intra-axonal ultrastructural changes associated with traumatically induced alteration in axolemmal permeability. Brain Res. 722, 1–11.
Pierce J. E.S., Trojanowski J. Q., Graham D. I., Smith D. H., and McIntosh T. K. (1996) Immunohistochemical characterization of alterations in the distribution of amyloid precursor proteins and amyloid β peptide following experimental brain injury in the rat. J. Neurosci. 16, 1083–1090.
Pilz P. (1983) Axonal injury in head injury. Acta Neurochir. (Wein) 32, 119–123.
Polymeropoulos M. H., Lavedan C., Leroy E., et al. (1997) Mutation in the alpha-synuclein gene identified in families with Parkinson’s disease. Science 276, 2045–2047.
Posmantur R. M., Newcomb J. K., Kampfl A., and Hayes R. L. (2000) Light and confocal microscopic studies of evolutionary changes in neurofilament proteins following cortical impact injury in the rat. Exp. Neurol. 161, 15–26.
Posmantur R., Hayes R. L., Dixon C. E., and Taft W. C. (1994) Neurofilament 68 and Neurofilament 200 protein levels decrease after traumatic brain injury. J. Neurotrauma 11, 533–545.
Povlishock J. T. and Becker D. P. (1985) Fate of reactive axonal swellings induced by head injury. Lab. Invest. 52, 540–552.
Povlishock J. T., Marmarou A., McIntosh T. K., Trojanowski J. Q., and Moroi J. (1997) Impact acceleration injury in the rat: Evidence for focal axolemmal change and related neurofilament sidearm alteration. J. Neuropathol. Exp. Neurol. 56, 347–359.
Pratico D., Reiss P., Tang L. X., et al. (2002) Local and systemic increase in lipid peroxidation after moderate experimental traumatic brain injury. J. Neurochem. 80, 894–898.
Raby C. A., Morganti-Kossmann M. C., Kossmann T., et al. (1998) Traumatic brain injury increases beta-amyloid peptide 1–42 in cerebrospinal fluid. J. Neurochem. 71, 2505–2509.
Rasmusson D. X., Brandt J., Martin D. B., and Folstein M. F. (1995) Head injury as a risk factor in Alzheimer’s disease. Brain Injury 3, 213–219.
Reichard R. R., White C. L., III, Hladik C. L., and Dolinak D. (2003) Beta-amyloid precursor protein staining in nonhomicidal pediatric medicolegal autopsies. J. Neuropathol. Exp. Neurol. 62, 237–247.
Roberts G. W., Gentleman S. M., Lynch A., and Graham D. I. (1991) βA4 amyloid protein deposition in brain after head trauma. Lancet 338, 1422–1423.
Saatman K. E., Abai B., Grosvenor A., et al. (2003) Traumatic axonal injury results in biphasic calpain activation and retrograde transport impairment in mice. J. Cereb. Blood Flow Metab. 23, 34–42.
Saatman K. E., Graham D. I., and McIntosh T. K. (1998) The neuronal cytoskeleton is at risk after mild and moderate brain injury. J. Neurotrauma 15, 1047–1058.
Schmidt M. L., Zhukareva V., Newell K. L., Lee V. M., and Trojanowski J. Q. (2001) Tau isoform profile and phosphorylation state in dementia pugilistica recapitulate Alzheimer’s disease. Acta Neuropathol. (Berlin) 101, 518–524.
Schofield P. W., Tang M., Marder K., et al. (1997) Alzheimer’s disease after remote head injury: an incidence study. J. Neurol. Neurosurg. Psychiat. 62, 119–124.
Selkoe D. J. and Wolfe M. S. (2000) In search of gamma-secretase: presenilin at the cutting edge. Proc. Natl. Acad. Sci USA 97, 5690–5692.
Sherriff F. E., Bridges L. R., and Sivaloganathan S. (1994) Early detection of axonal injury after human head trauma using immunocytochemistry for β-amyloid precursor protein. Acta Neuropathol. 87, 55–62.
Smith D. H., Chen X. H., Iwata A., and Graham D. I. (2003) Amyloid beta accumulation in axons after traumatic brain injury in humans. J. Neurosurg. 98, 1072–1077.
Smith D. H. and Meaney D. F. (2000) Axonal damage in traumatic brain injury. Neuroscientist 6, 483–495.
Smith D. H., Chen X.-H., Nonaka M., et al. (1999) Accumulation of amyloid β and tau and the formation of neurofilament inclusions following diffuse brain injury in the pig. J. Neuropathol. Exp. Neurol. 58, 982–992.
Smith D. H., Nakamura M., McIntosh T. K., et al. (1998) Brain trauma induces massive hippocampal neuron death linked to a surge in β-amyloid levels in mice overexpressing mutant amyloid precursor protein. Am. J. Pathol. 153, 1005–1110.
Soriano S., Lu D. C., Chandra S., Pietrzik C. U., and Koo E. H. (2001) The amyloidogenic pathway of amyloid precursor protein (APP) is independent of its cleavage by caspases. J. Biol. Chem. 276, 29045–29050.
Sosin D. M., Sniezek J. E., and Waxweiler R. J. (1995) Trends in death associated with traumatic brain injury, 1979 through 1992. JAMA 273, 1778–1780.
Sosin D. M., Sacks J. J., and Smith S. M. (1989) Head injury-associated deaths in the United States from 1979 to 1986. JAMA 262, 2251–2255.
Souza J. M., Giasson B. I., Chen Q., Lee V. M., and Ischiropoulos H. (2000a) Dityrosine cross-linking promotes formation of stable alpha-synuclein polymers. Implication of nitrative and oxidative stress in the pathogenesis of neurodegenerative synucleinopathies. J. Biol. Chem. 275, 18344–18349.
Souza J. M., Giasson B. I., Lee V. M., and Ischiropoulos H. (2000b) Chaperone-like activity of synucleins. FEBS Lett. 474, 116–119.
Spillantini M. G., Crowther R. A., Jakes R., Hasegawa M., and Goedert M. (1998) alpha-Synuclein in filamentous inclusions of Lewy bodies from Parkinson’s disease and dementia with Lewy bodies. Proc. Natl. Acad. Sci. USA 95, 6469–6473.
Spillantini M. G., Schmidt M. L., Lee V. M., et al. (1997) Alpha-synuclein in Lewy bodies. Nature 388, 839–840.
Stefanis L., Kholodilov N., Rideout H. J., Burke R. E., and Greene L. A. (2001) Synuclein-1 is selectively up-regulated in response to nerve growth factor treatment in PC12 cells. J. Neurochem. 76, 1165–1176.
Stern M. B. (1991) Head trauma as a risk factor for Parkinson’s disease. Mov. Disord. 6, 95–97.
Stone J. R., Okonkwo D. O., Singleton R. H., et al. (2002) Caspase-3-mediated cleavage of amyloid precursor protein and formation of amyloid Beta peptide in traumatic axonal injury. J. Neurotrauma 19, 601–614.
Stone J. R., Singleton R. H., and Povlishock J. T. (2001) Intra-axonal neurofilament compaction does not evoke local axonal swelling in all traumatically injured axons. Exp. Neurol. 172, 320–331.
Tanner C. M., Ottman R., Goldman S. M., et al. (1999) Parkinson disease in twins: an etiologic study. JAMA 281, 341–346.
Teasdale G. M., Nicoll J. A., Murray G., and Fiddes M. (1997) Association of apolipoprotein E polymorphism with outcome after head injury. Lancet 350, 1069–1071.
Thiruchelvam M., Richfield E. K., Baggs R. B., Tank A. W., and Cory-Slechta D. A. (2000) The nigrostriatal dopaminergic system as a preferential target of repeated exposures to combined paraquat and maneb: implications for Parkinson’s disease. J. Neurosci. 20, 9207–9214.
Tokuda T., Ikeda S., Yanagisawa N., Ihara Y., and Glenner G. G. (1991) Re-examination of ex-boxers’ brains using immunohistochemistry with antibodies to amyloid β-protein and tau protein. Acta Neuropathol. 82, 281–285.
Trojanowski J. Q. and Lee V. M. (2002) Parkinson’s disease and related synucleinopathies are a new class of nervous system amyloidoses. Neurotoxicology 23, 457–460.
Trojanowski J. Q., Schmidt M. L., Shin R. W., et al. (1993) Altered Tau and neurofilament proteins in neurodegenerative diseases: diagnostic implications for Alzheimer’s disease and Lewy body dementias. Brain Pathol. 3, 45–54.
Tu P. H., Galvin J. E., Baba M., et al. (1998) Glial cytoplasmic inclusions in white matter oligodendrocytes of multiple system atrophy brains contain insoluble alpha-synuclein. Ann. Neurol. 44, 415–422.
Tu P.-H., Robinson K. A., Snoo F., et al. (1997) Selective degeneration of Purkinje cells with Lewy body-like inclusions in aged NFHLACZ transgenic mice. J. Neurosci. 17, 1064–1074.
Tu P.-H., Elder G., Lazzarini R. A., et al. (1995) Over-expression of the human NFM subunit in transgenic mice modifies the level of endogenous NFL and the phosphorylation state of NFH subunits. J. Cell Biol. 129, 1629–1640.
Uryu K., Giasson B. I., Longhi L., et al. (2003) Age-dependent synuclein pathology following traumatic brain injury in mice. Exp. Neurol, in press.
Uryu K., Laurer H., McIntosh T., et al. (2002) Repetitive mild brain trauma accelerates Abeta deposition, lipid peroxidation, and cognitive impairment in a transgenic mouse model of Alzheimer amyloidosis. J. Neurosci. 22, 446–454.
Uversky V. N., Li J., and Fink A. L. (2001) Evidence for a partially folded intermediate in alpha-synuclein fibril formation. J. Biol. Chem. 276, 10737–10744.
Van Den Heuvel C., Finnie J. W., Blumbergs P. C., et al. (2000) Upregulation of neuronal amyloid precursor protein (APP) and APP mRNA following magnesium sulphate (MgSO4) therapy in traumatic brain injury. J. Neurotrauma 17, 1041–1053.
Vassar R., Bennett B. D., Babu-Khan S., et al. (1999) Beta-secretase cleavage of Alzheimer’s amyloid precursor protein by the transmembrane aspartic protease BACE. Science 286, 735–741.
Xu Z., Cork L. C., Griffin J. W., and Cleveland D. W. (1993) Increased expression of neurofilament subunit NF-L produces morphological alterations that resemble the pathology of human motor neuron disease. Cell 73, 23–33.
Yaghmai A. and Povlishock J. T. (1992) Traumatically induced reactive change as visualized through the use of monoclonal antibodies targeted to neurofilament subunits. J. Neuropathol. Exp. Neurol. 51, 158–176.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Smith, D.H., Uryu, K., Saatman, K.E. et al. Protein accumulation in traumatic brain injury. Neuromol Med 4, 59–72 (2003). https://doi.org/10.1385/NMM:4:1-2:59
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1385/NMM:4:1-2:59