A Novel, Ultrasensitive Assay for Tau: Potential for Assessing Traumatic Brain Injury in Tissues and Biofluids
Abstract
Traumatic brain injury (TBI) is a cause of death and disability and can lead to tauopathy-related dementia at an early age. Pathologically, TBI results in axonal injury that is coupled to tau hyperphosphorylation, leading to microtubule instability and tau-mediated neurodegeneration. This suggests that the forms of this protein might serve as neuroinjury-related biomarkers for diagnosis of injury severity and prognosis of the neurological damage prior to clinical expression. We initially determined whether we could detect tau in body fluids using a highly sensitive assay. We used a novel immunoassay, enhanced immunoassay using multi-arrayed fiberoptics (EIMAF) either alone or in combination with rolling circle amplification (a-EIMAF) for the detection of total (T) and phosphorylated (P) tau proteins from brains and biofluids (blood, CSF) of rodents following controlled cortical impact (CCI) and human patients post severe TBI (sTBI). This assay technology for tau is the most sensitive to date with a detection limit of approximately 100 ag/mL for either T-tau and P-tau. In the rodent models, T-tau and P-tau levels in brain and blood increased following CCI during the acute phase and remained high during the chronic phase (30 d). In human CSF samples, T-tau and P-tau increased during the sampling period (5–6 d). T-tau and P-tau in human serum rose during the acute phase and decreased during the chronic stage but was still detectable beyond six months post sTBI. Thus, EIMAF has the potential for assessing both the severity of the proximal injury and the prognosis using easily accessible samples.
Get full access to this article
View all available purchase options and get full access to this article.
References
1.
Chiu W.T., Huang S.J., Tsai S.H., Lin J-W., Tsai M-D., and Lin T-J. (2007). The impact of time, legislation, and geography on the epidemiology of traumatic brain injury. J. Clin. Neurosci. 14, 930–935.
2.
Clinton J., Ambler M.W., and Roberts G.W. (1991). Post-traumatic Alzheimer's disease: preponderance of a single plaque type. Neuropathol. Appl. Neurobiol. 17, 69–74.
3.
Mortimer J.A., Van Duijn C.M., Chandra V., Fratiglioni L., Graves A.B., Heyman A., Jorm A.F., Kokmen E., Rocca W.A., Shalat S.L., Soininen H., and Hofman A. (1991). Head trauma as a risk factor for Alzheimer's disease: a collaborative re-analysis of case-control studies. EURODEM Risk Factors Research Group. Int. J. Epidemiol. 20, S28–S35.
4.
Breteler M.M., Claus J.J., Van Duijn C.M., Launer L.J., and Hofman A. (1992). Epidemiology of Alzheimer's disease. Epidemiol Rev 14, 59–82.
5.
Mayeux R., Ottman R., Tang M.X., Noboa-Bauza L., Marder K., Gurland B., and Stem Y. (1993). Genetic susceptibility and head injury as risk factors for Alzheimer's disease among community-dwelling elderly persons and their first-degree relatives. Ann. Neurol. 33, 494–501.
6.
Guo Z., Cupples L.A., Kurz A., Auerbach S.H., Volicer L., Chui H., Green R.C., Sadovnick A.D., Duara R., DeCarll C., Johnson K., Go R.C., Growdon J.H., Haines J.L., Kukull W.A., and Farrer L.A. (2000). Head injury and the risk of AD in the MIRAGE study. Neurology 54, 1316–1323.
7.
Plassman B.L., Havlik R.J., Steffens D.C., Helms M.J., Newman T.N., Drosdick D., Philips C., Gau B.A., Welsh-Bohmer K.A., Burke J.R., Guralnik J., and Breitner J.C.S. (2000). Documented head injury in early adulthood and risk of Alzheimer's disease and other dementias. Neurology 55, 1158–1166.
8.
Johnson V.E., Stewart W., and Smith D.H. (2010). Traumatic brain injury and amyloid-beta pathology: a link to Alzheimer's disease? Nat. Rev. Neurosci. 11, 361–370.
9.
Magnoni S., and Brody D.L. (2010). New perspectives on amyloid-beta dynamics after acute brain injury: moving between experimental approaches and studies in the human brain. Arch. Neurol. 67, 1068–1073.
10.
Li L.M., Menon D.K., and Janowitz T. (2014). Cross-sectional analysis of data from the U.S. clinical trials database reveals poor translational clinical trial effort for traumatic brain injury, compared with stroke. PLoS One 9, e84336.
11.
Raabe A., Grolms C., Sorge O., Zimmermann M., and Seifert V., 1999. Serum S-100B protein in severe head injury. Neurosurgery 45, 477–483.
12.
Woertgen C., Rothoerl R., Metz C., and Brawanski A. (1999). Comparison of clinical, radiologic, and serum marker as prognostic factors after severe head injury. J. Trauma 47, 1126–1130.
13.
Franz G., Beer R., Kampfl A., Engelhardt K., Schmutzhard E., Ulmer H., and Delsenhammer F. (2003). Amyloid beta 1–42 and tau in cerebrospinal fluid after severe traumatic brain injury. Neurology 60, 1457–1461.
14.
Vos P.E., Lamers K.J., Hendriks J.C., van Haaren M., Beems T., Zimmerman C., van Geel W., de Reus H., Blert J., and Verbeek M.M. (2004). Glial and neuronal proteins in serum predict outcome after severe traumatic brain injury. Neurology 62, 1303–1310.
15.
Bulut M., Koksal O., Dogan S., Bolca N., Ozguc H., Korfali E., Ilcolet Y.O., and Parkiak M. (2006). Tau protein as a serum marker of brain damage in mild traumatic brain injury: preliminary results. Adv. Ther. 23, 12–22.
16.
Kavalci C., Pekdemir M., Durukan P., Ilhan N., Yildiz M., Serhatlioglu S., and Seckin D. (2007). The value of serum tau protein for the diagnosis of intracranial injury in minor head trauma. Am. J. Emerg. Med. 25, 391–395.
17.
Korfias S., Stranjalis G., Boviatsis E., Psachoulia C., Jullien G., Gregson B., Mendelow A.D., and Sakas D.E. (2007). Serum S-100B protein monitoring in patients with severe traumatic brain injury. Intensive Care Med. 33, 255–260.
18.
Papa L., Akinyi L., Liu M.C., Pineda J.A., Tepas J.J. III, Oli M.W., Zheng W., Robinson G., Robicsek S.A., Gabrielli A., Heaton S.C., Hannay H.J., Demery J.A., Brophy G.M., Layon J., Robertson C., Hayes R.L., and Wang K.K.W. (2010). Ubiquitin C-terminal hydrolase is a novel biomarker in humans for severe traumatic brain injury. Crit. Care Med. 38, 138–144.
19.
Mondello S., Robicsek S.A., Gabrielli A., Brophy G.M., Papa L., Tepas J., Robertson C., Buki A., Scharf D., Jixiang M., Akinyi L., Muller U., Wang K.K.W., and Hayes R.L. (2010). AlphaII-spectrin breakdown products (SBDPs): diagnosis and outcome in severe traumatic brain injury patients. J. Neurotrauma 27, 1203–1213.
20.
Mondello S., Jeromin A., Buki A., Bullock R., Czeiter E., Kovacs N., Barzo P., Schmid K., Tortella F., Wang K.K., and Hayes R.L. (2012). Glial neuronal ratio: a novel index for differentiating injury type in patients with severe traumatic brain injury. J. Neurotrauma 29, 1096–1104.
21.
Trojanowski J.Q., Schuck T., Schmidt M.L., and Lee V.M. (1989). Distribution of tau proteins in the normal human central and peripheral nervous system. J. Histochem. Cytochem. 37, 209–215.
22.
Sivanandam T.M. and Thakur M.K. (2012). Traumatic brain injury: a risk factor for Alzheimer's disease. Neurosci. Biobehav. Rev. 36, 1376–1381.
23.
Alonso A., Zaidi T., Novak M., Grundke-Iqbal I., and Iqbal K. (2001). Hyperphosphorylation induces self-assembly of tau into tangles of paired helical filaments/straight filaments. Proc. Natl. Acad. Sci. U.S.A. 98, 6923–6928.
24.
Feijoo C., Campbell D.G., Jakes R., Goedert M., and Cuenda A. (2005). Evidence that phosphorylation of the microtubule-associated protein Tau by SAPK4/p38delta at Thr50 promotes microtubule assembly. J. Cell Sci. 118, 397–408.
25.
Morris M., Maeda S., Vossel K., and Mucke L. (2011). The many faces of tau. Neuron 70, 410–426.
26.
Blennow K. and Hampel H. (2003). CSF markers for incipient Alzheimer's disease. Lancet Neurol. 2, 605–613.
27.
Selkoe D. J. and Schenk D. (2003). Alzheimer's disease: molecular understanding predicts amyloid-based therapeutics. Ann. Rev. Pharmacol. Toxicol. 43, 545–584.
28.
Goedert M., Jakes R., Crowther R.A., Cohen P., Vanmechelen E., Vandermeeren M., and Cras P. (1994). Epitope mapping of monoclonal antibodies to the paired helical filaments of Alzheimer's disease: identification of phosphorylation sites in tau protein. Biochem. J. 301, 871–877.
29.
Davies P., 2000. Characterization and use of monoclonal antibodies to tau and paired helical filament tau. Methods Mol. Med. 32, 361–373.
30.
Sato S., Cerny R.L., Buescher J.L., and Ikezu T. (2006). Tau-tubulin kinase 1 (TTBK1), a neuron-specific tau kinase candidate, is involved in tau phosphorylation and aggregation. J. Neurochem. 9, 1573–1584.
31.
Hanger D.P., Byers H.L., Wray S., Leung K-Y., Saxton M.J., Seereeram A., Reynolds C.H., Ward M.A., and Anderton B.H. (2007). Novel phosphorylation sites in tau from Alzheimer brain support a role for casein kinase 1 in disease pathogenesis. J. Biochem. 282, 23645–23654.
32.
Wang J-Z., Grundke-Iqbal I., and Iqbal K. (2007). Kinases and phosphatases and tau sites Involved in Alzheimer neurofibrillary degeneration. Eur. J. Neurosci. 25, 59–68
33.
Mattson N., Zegers I., Andreasson U., Bjerke M., Blankenstein M.A., Bowser R., Carrillo M.C., Gobomd J., Heath T., Jenkins R., Jeromin A., Kaplow J., Kidd D., Laterza O.F., Lockhart A., Lunn M.P., Martone R.L., Mills K., Pannee J., Ratcliffe M., Shaw L.M., Simon A.J., Soares H., Teunissen C.E., Verbeek M.M., Umek R.M., Vanderstichele H., Zetterberg H., Blennow K., and Portelius E. (2012). Reference measurement procedures for Alzheimer's disease cerebrospinal fluid biomarkers: definitions and approaches with focus on amyloid beta 42. Biomark. Med. 6, 409–417.
34.
Ost M., Nylen K., Csajbok L., Ohrfelt A.O., Tullberg M., Wikkelso C., Nellgard P., Rosengren L., Blennow K., and Nellgard B. (2006). Initial CSF total tau correlates with 1-year outcome in patients with traumatic brain injury. Neurology 67, 1600–1604.
35.
Liliang P.C., Liang C.L., Weng H.C., Lu K., Wang K.W., Chen H.J., and Chuang J.H. (2010). Tau proteins in serum predict outcome after severe traumatic brain injury. J. Surg. Res. 160, 302–307.
36.
Rostami E., Davidsson J., Ng K.C., Lu J., Gyorgy A., Walker J., Wingo D., Plantman S., Bellander B., Agoston D.V., and Risling M. (2012). A model for mild traumatic brain injury that induces limited transient memory impairment and increased levels of axon related serum biomarkers. Front. Neurol. 3, 115.
37.
Corsellis J.A., Bruton C.J., and Freeman-Browne D. (1973). The aftermath of boxing. Psychol. Med. 3, 270–303.
38.
Roberts G.W., Allsop D., and Bruton C. (1990). The occult aftermath of boxing. J Neurol Neurosurg. Psychiatry 53, 373–378.
39.
Dale G.E., Leigh P.N., Luthert P., Anderton B.H., and Roberts G.W. (1991). Neurofibrillary tangles in dementia pugilistica are ubiquitinated. J. Neurol. Neurosurg. Psychiatry 54, 116–118.
40.
Geddes J.F., Vowles G.H., Nicoll J.A., and Revesz T. (1999). Neuronal cytoskeletal changes are an early consequence of repetitive head injury. Acta Neuropathol. 98, 171–178.
41.
McKee A.C., Cantu R.C., Nowinski C.J., Hedley-Whyte E.T., Gavett B.E., Budson A.E., Santini V.E., Lee H.S., Kubilus C.A., and Stern R.A. (2009). Chronic traumatic encephalopathy in athletes: progressive tauopathy after repetitive head injury. J. Neuropathol. Exp. Neurol. 68, 709–735.
42.
McKee A.C., Stein T.D., Nowinski C.J., Stern R.A., Daneshvar D.H., Alvarez V.E., Lee H.S., Hall G., Wojtowicz S.M., Baugh C.M., Riley D.O., Kubilus C.A., Cormier K.A., Jacobs M.A., Martin B.R., Abraham C.R., Ikezu T., Reichard R.R., Wolozin B.L., Budson A.E., Goldstein L.E., Kowalk N.W., and Cantu R.C. (2013). The spectrum of disease in chronic traumatic encephalopathy. Brain 136, 43–64.
43.
Jordan B.D., Kanik A.B., Horwich M.S., Sweeney D., Relkin N.R., Petito C.K., and Gandy S. (1995). Apolipoprotein E epsilon 4 and fatal cerebral amyloid angiopathy associated with dementia pugilistica. Ann. Neurol. 38, 698–699.
44.
McKenzie K.J., McLellan D.R., Gentleman S.M., Maxwell W.L., Gennarelli T.A., and Graham D.I. (1996). Is beta-APP a marker of axonal damage in short-surviving head injury? Acta Neuropathol. 92, 608–613.
45.
Nowak L.A., Smith G.G., and Reyes P.F. (2009). Dementia in a retired world boxing champion: case report and literature review. Clin. Neuropathol. 28, 275–280.
46.
Omalu B.I., Fitzsimmons R.P., Hammers J., and Bailes J. (2010). Chronic traumatic encephalopathy in a professional american wrestler. J. Forensic Nurs. 6, 130–136.
47.
Smith D.H., Johnson V.E., and Stewart W. (2013). Chronic neuropathologies of single and repetitive TBI: substrates of dementia? Nat. Rev. Neurol. 9, 211–221.
48.
Gabbita S.P., Scheff S.W., Menard R.M., Roberts K., Fugaccia I., and Zemlan F.P. (2005). Cleaved-tau: a biomarker of neuronal damage after traumatic brain injury. J. Neurotrauma 22, 83–94.
49.
Liliang P.C., Liang C.L., Lu K., Wang K.W., Weng H.C., Hsieh C.H., Tsai Y-D., and Chen H-J. (2010). Relationship between injury severity and serum tau protein levels in traumatic brain injured rats. Resuscitation 81, 1205–1208.
50.
Chang B., Gray P., Piltch M., Bulgin M.S., Sorensen-Melson S., Miller M.W., Davies P., Brown D.R., Coughlin D.R., and Rubenstein R. (2009). Surround optical fiber immunoassay (SOFIA): more than an ultra-sensitive assay for PrP detection. J. Virol. Methods 159, 15–22.
51.
Rubenstein R., Chang B., Gray P., Piltch M., Bulgin M.S., Sorensen-Melson S., and Miller M.W. (2010). A novel method for preclinical detection of PrPSc in blood. J. Gen. Virol. 91, 1883–1892.
52.
Rubenstein R., Chang B., Gray P., Piltch M., Bulgin M., Sorensen-Melson S., and Miller M.W. (2011). Prion disease detection, PMCA kinetics, and IgG in urine from naturally/experimentally infected scrapie sheep and preclinical/clinical CWD deer. J. Virol. 85, 9031–9038.
53.
Rubenstein R., Bulgin M.S., Chang B., Sorensen-Melson S., Petersen R.B., and LaFauci G. (2012). PrPSc detection and infectivity in semen from scrapie-infected sheep. J. Gen. Virol. 93, 1375–1383.
54.
Rubenstein R. and Chang B. (2013). Re-Assessment of PrPSc distribution in sporadic and variant CJD. PLoS ONE 8, e66352.
55.
Acker C.M., Forest S.K., Zinkowski R., Davies P., and d'Abramo C. (2013). Sensitive quantitative assays for tau and phosphor-tau in transgenic mouse models. Neurobiol. Aging 34, 338–350.
56.
Schweitzer B., Wiltshire S., Lambert J., O'Malley S., Kukanskia K., Zhu Z., Kingsmore S.F., Lizardi P.M., and Ward D.C. (2000). Immunoassays with rolling circle DNA amplification: a versatile platform for ultrasensitive antigen detection. Proc. Natl. Acad. Sci. U.S.A. 97, 10113–10119.
57.
Rankin C.A., Sun Q., and Gamblin T.C. (2007). Tau phosphorylation by GSK-3β promotes tangle-like filament morphology. Mol. Neurodegen. 2, 12.
58.
Lewis J., McGowan E., Rockwood J., Melrose H., Nacharaju P., Van Slegtenhorst M., Gwinn-Hardy K., Murphy M.P., Baker M., Yu X., Duff K., Hardy J., Corral A., Lin W-L., Yen S-H., Dickson D.W., Davies P., and Hutton M. (2000). Neurofibrillary tangles, amyotrophy and progressive motor disturbance in mice expressing mutant (P301L) tau protein. Nat. Genet. 25, 402–405.
59.
Dawson H.N., Ferreira A., Eyster M.V., Ghoshal N., Binder L.I., and Vitek M.P. (2001). Inhibition of neuronal maturation in primary hippocampal neurons from tau deficient mice. J. Cell Sci. 114, 1179–1187.
60.
Grundke-Iqbal I., Iqbal K., Quinlan M., Tung Y.C., Zaidi M.S., and Wisniewski H.M. (1986). Microtubule-associated protein tau. A component of Alzheimer paired helical filaments. J. Biol. Chem. 261, 6084–6089.
61.
Nukina N. and Ihara Y. (1986). One of the antigenic determinants of paired helical filaments is related to tau protein. J. Biochem. 99, 1541–1544.
62.
Wood J.G., Mirra S.S., Pollock N.J., and Binder L.I. (1986). Neurofibrillary tangles of Alzheimer disease share antigenic determinants with the axonal microtubule-associated protein tau. Proc. Natl. Acad. Sci. U.S.A. 83, 4040–4043.
63.
Kondo J., Honda T., Mori H., Hamada Y., Miura R., Ogawara M., and Ihara Y. (1988). The carboxyl third of tau is tightly bound to paired helical filaments. Neuron 1, 827–834.
64.
Lee V.M., Balin B.J., Otvos L. Jr., and Trojanowski J.Q. (1991). A68: a major subunit of paired helical filaments and derivatized forms of normal Tau. Science 251, 675–678.
65.
Lee V.M., Goedert M., and Trojanowski J.Q. (2001). Neurodegenerative tauopathies. Ann. Rev. Neurosci. 24, 1121–1159.
66.
Omalu B., Bailes J., Hamilton R.L., Kamboh M.I., Hammers J., Case M., and Fitzsimmons R. (2011). Emerging histomorphologic phenotypes of chronic traumatic encephalopathy in American athletes. Neurosurgery 69, 173–183.
67.
Rajput A., Dickson D.W., Robinson C.A., Ross O.A., Dachsel J.C., Lincoln S.J., Cobb S.A., Rajput M.L., and Farrer M.J. (2006). Parkinsonism, Lrrk2 G2019S, and tau neuropathology. Neurology 67, 1506–1508.
68.
Santpere G. and Ferrer I. (2009). LRRK2 and neurodegeneration. Acta Neuropathol. 117, 227–246.
69.
Ihara Y. (2001). PHF and PHF-like fibrils–cause or consequence? Neurol. Aging 22, 123–126.
70.
Giannakopoulos P., Herrmann F.R., Bussiere T., Bouras C., Kovari E., Perl D.P., Morrison J.H., Gold G., and Hof P.R. (2003). Tangle and neuron numbers, but not amyloid load, predict cognitive status in Alzheimer's disease. Neurology 60, 1495–1500.
71.
Shahim P., Tegner Y., Wilson D.H., Randall J., Skillback T., Pazooki D., Kallberg B., Blennow K., and Zetterberg H. (2014). Blood biomarkers for brain injury in concussed professional ice hockey players. JAMA Neurol. 71, 684–692.
72.
Woertgen C., Rothoerl R.D., and Brawanski A. (2001). Neuron-specific enolase serum levels after controlled cortical impact injury in the rat. J. Neurotrauma 18, 569–573.
73.
Woertgen C., Rothoerl R.D., Wiesmann M., Missler U., and Brawanski A. (2002). Glial and neuronal serum markers after controlled cortical impact injury in the rat. Acta Neurochir. Suppl 81, 205–207.
74.
Rothermundt M., Peters M., Prehn J.H., and Arolt V. (2003). S100B in brain damage and neurodegeneration. Microsc. Res. Tech. 60, 614–632.
75.
Ross S.A., Cunningham R.T., Johnston C.F., and Rowlands B.J. (1996). NSE as an aid to outcome prediction in head injury. Br. J. Neurosurg. 10, 471–476.
76.
Pelinka L.E., Kroepfl A., Schmidhammer R., Krenn M., Buchinger W., Redl H., and Raabe A. (2004). Glial fibrillary acidic protein in serum after traumatic brain injury and multiple trauma. J. Trauma 57, 1006–1012.
77.
Honda M., Tsuruta R., Kaneko T., Kasaoka S., Yagi T., Todani M., Fujita M., Izumi T., and Meekawa T. (2010). Serum glial fibrillary acidic protein is a highly specific biomarker for traumatic brain injury in humans compared with S-100B and neuron-specific enolase. J. Trauma 69, 104–109.
78.
Papa L., Lewis L.M., Falk J.L., Zhang Z., Silvestri S., Giordano P., Brophy G.M., Demery J.A., Dixit N.K., Ferguson I., Liu M.C., Mo J., Akinyi L., Schmid K., Mondello S., Robertson C.S., Tortella F.C., Hayes R.L., and Wang K.K.W. (2012a). Elevated levels of serum glial fibrillary acidic protein breakdown products in mild and moderate traumatic brain injury are associated with intracranial lesions and neurosurgical intervention. Ann. Emerg. Med. 59, 471–483.
79.
Okonkwo D.O., Yue J.K., Puccio A.M., Panczykowski D.M., Inoue T., McMahon P.J., Sorani M.D., Yuh E.L., Lingsma H.F., Maas A.I.R., Valadka A.B., Manley G.T., and Transforming Research and Clinical Knowledge in Traumatic Brain Injury investigators including, Casey S.S., Cheong M., Cooper S.R., Dams-O'Connor K., Gordon W.A., Hricik A.J., Hochberger K., Menon D.K., Mukherjee P., Sinha T.K., Schnyer D.M., and Vassar M.J. (2013). GFAP-BDP as an acute diagnostic marker in traumatic brain injury: eesults from the prospective transforming research and clinical knowledge in traumatic brain injury study. J. Neurotrauma 30, 1490–1497.
80.
Papa L., Lewis L.M., Silvestri S., Falk J.L., Giordano P., Brophy G.M., Demery J.A., Liu M.C., Mo J., Akinyi L., Mondello S., Schmid K., Robertson C., Tortella F.C., Hayes R.L., and Wang K.K.W. (2012b). Serum levels of ubiquitin C-terminal hydrolase distinguish mild traumatic brain injury from trauma controls and are elevated in mild and moderate traumatic brain injury patients with intracranial lesions and neurosurgical intervention. J. Trauma Acute Care Surg. 72, 1335–1344.
81.
Diaz-Arrastia R., Wang K.K.W., Papa L., Sorani M.D., Yue J.K., Puccio A.M., McMahon P.J., Inoue T., Yuh E.L., Lingsma H.F., Maas A.I.R., Valadka A.B., Okonkwo D.O., Manley G.T., and the TRACK-TBI Investigators including Casey S.S., Cheong M., Cooper S.R., Dams-O'Connor K., Gordon W.A., Hricik A.J., Menon D.K., Mukherjee P., Schnyer D.M., Sinha T.K., and Vassar M.J. (2014). Acute biomarkers of traumatic brain injury: relationship between plasma levels of ubiquitin C-terminal hydrolase-L1 (UCH-L1) and glial fibrillary acidic protein (GFAP). J. Neurotrauma 31, 19–25.
82.
Ma M., Lindsell C.J., Rosenberry C.M., Shaw G.J., and Zemlan F.P. (2008). Serum cleaved tau does not predict postconcussion syndrome after mild traumatic brain injury. Am. J. Emerg. Med. 26, 763–768.
83.
Fleminger S., Oliver D.L., Lovestone S., Rabe-Hesketh S., and Giora A. (2003). Head injury as a risk factor for Alzheimer's disease: the evidence 10 years on; a partial replication. J. Neurol. Neurosurg. Psychiatry 74, 857–862.
84.
Johnson V.E., Stewart W., and Smith D.H. (2012). Widespread tau and amyloid-Beta pathology many years after a single traumatic brain injury in humans. Brain Pathol. 22, 142–149.
85.
Smith C., Graham D.I., Murray L.S., and Nicoll J.A. (2003). Tau immunohistochemistry in acute brain injury. Neuropathol. Appl. Neurobiol. 29, 496–502.
86.
Uryu K., Chen X.H., Martinez D., Browne K.D., Johnson V.E., Graham D.I., Lee V.M-Y., Trojanowski J.Q., and Smith D.H. (2007). Multiple proteins implicated in neurodegenerative diseases accumulate in axons after brain trauma in humans. Exp. Neurol. 208, 185–192.
87.
Czeiter E., Mondello S., Kovacs N., Sandor J., Gabrielli A., Schmid K., Tortella F., Wang K.K.W., Hayes R.L., Barzo P., Ezer E., Doczi T., and Buki A. (2012). Brain injury biomarkers may improve the predictive power of the IMPACT outcome calculator. J. Neurotrauma 29, 177–1778.
Information & Authors
Information
Published In
Copyright
Copyright 2015, Mary Ann Liebert, Inc.
History
Published in print: March 1, 2015
Published ahead of print: 23 December 2014
Published online: 1 September 2014
Topics
Authors
Author Disclosure Statement
No competing financial interests exist.
Metrics & Citations
Metrics
Citations
Export Citation
Export citation
Select the format you want to export the citations of this publication.
View Options
Get Access
Access content
To read the fulltext, please use one of the options below to sign in or purchase access.⚠ Society Access
If you are a member of a society that has access to this content please log in via your society website and then return to this publication.