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Published Online: 12 February 2011

Modulation of ABCA1 by an LXR Agonist Reduces Beta-Amyloid Levels and Improves Outcome after Traumatic Brain Injury

Publication: Journal of Neurotrauma
Volume 28, Issue Number 2

Abstract

Traumatic brain injury (TBI) increases brain beta-amyloid (Aβ) in humans and animals. Although the role of Aβ in the injury cascade is unknown, multiple preclinical studies have demonstrated a correlation between reduced Aβ and improved outcome. Therefore, therapeutic strategies that enhance Aβ clearance may be beneficial after TBI. Increased levels of ATP-binding cassette A1 (ABCA1) transporters can enhance Aβ clearance through an apolipoprotein E (apoE)-mediated pathway. By measuring Aβ and ABCA1 after experimental TBI in C57BL/6J mice, we found that Aβ peaked early after injury (1–3 days), whereas ABCA1 had a delayed response (beginning at 3 days). As ABCA1 levels increased, Aβ levels returned to baseline levels—consistent with the known role of ABCA1 in Aβ clearance. To test if enhancing ABCA1 levels could block TBI-induced Aβ, we treated TBI mice with the liver X-receptor (LXR) agonist T0901317. Pre- and post-injury treatment increased ABCA1 levels at 24 h post-injury, and reduced the TBI-induced increase in Aβ. This reduction in Aβ was not due to decreased amyloid precursor protein processing, or a shift in the solubility of Aβ, indicating enhanced clearance. T0901317 also limited motor coordination deficits in injured mice and reduced brain lesion volume. These data indicate that activation of LXR can reduce Aβ accumulation after TBI, and is accompanied by improved functional recovery.

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References

Abrahamson E.E.Ikonomovic M.D.Ciallella J.R.Hope C.E.Paljug W.R.Isanski B.A.Flood D.G.Clark R.S.DeKosky S.T.2006. Caspase inhibition therapy abolishes brain trauma-induced increases in Abeta peptide: implications for clinical outcomeExp. Neurol.197437-450. Abrahamson, E.E., Ikonomovic, M.D., Ciallella, J.R., Hope, C.E., Paljug, W.R., Isanski, B.A., Flood, D.G., Clark, R.S., and DeKosky, S.T. (2006). Caspase inhibition therapy abolishes brain trauma-induced increases in Abeta peptide: implications for clinical outcome. Exp. Neurol. 197, 437–450.
Abrahamson E.E.Ikonomovic M.D.Dixon C.E.Dekosky S.T.2009. Simvastatin therapy prevents brain trauma-induced increases in beta-amyloid peptide levelsAnn. Neurol.66407-414. Abrahamson, E.E., Ikonomovic, M.D., Dixon, C.E., and Dekosky, S.T. (2009). Simvastatin therapy prevents brain trauma-induced increases in beta-amyloid peptide levels. Ann. Neurol. 66, 407–414.
Bazarian J.J.Cernak I.Noble-Haeusslein L.Potolicchio S.Temkin N.2009. Long-term neurologic outcomes after traumatic brain injuryJ. Head Trauma Rehabil.24439-451. Bazarian, J.J., Cernak, I., Noble-Haeusslein, L., Potolicchio, S., and Temkin, N. (2009). Long-term neurologic outcomes after traumatic brain injury. J. Head Trauma Rehabil. 24, 439–451.
Blasko I.Beer R.Bigl M.Apelt J.Franz G.Rudzki D.Ransmayr G.Kampfl A.Schliebs R.2004. Experimental traumatic brain injury in rats stimulates the expression, production and activity of Alzheimer's disease beta-secretase (BACE-1)J. Neural Transm.111523-536. Blasko, I., Beer, R., Bigl, M., Apelt, J., Franz, G., Rudzki, D., Ransmayr, G., Kampfl, A., and Schliebs, R. (2004). Experimental 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.
Boyd-Kimball D.Sultana R.Mohmmad-Abdul H.Butterfield D.A.2004. Rodent Abeta(1–42) exhibits oxidative stress properties similar to those of human Abeta(1–42): Implications for proposed mechanisms of toxicityJ. Alzheimers Dis.6515-525. Boyd-Kimball, D., Sultana, R., Mohmmad-Abdul, H., and Butterfield, D.A. (2004), Rodent Abeta(1–42) exhibits oxidative stress properties similar to those of human Abeta(1–42): Implications for proposed mechanisms of toxicity. J. Alzheimers Dis. 6, 515–525.
Brera B.Serrano A.de Ceballos M.L.2000. Beta-amyloid peptides are cytotoxic to astrocytes in culture: a role for oxidative stressNeurobiol. Dis.7395-405. Brera, B., Serrano, A., and de Ceballos, M.L. (2000). Beta-amyloid peptides are cytotoxic to astrocytes in culture: a role for oxidative stress. Neurobiol. Dis. 7, 395–405.
Burns M.Gaynor K.Olm V.Mercken M.LaFrancois J.Wang L.Mathews P.M.Noble W.Matsuoka Y.Duff K.2003. Presenilin redistribution associated with aberrant cholesterol transport enhances β-amyloid production in vivoJ. Neurosci.235645-5649. Burns, M., Gaynor, K., Olm, V., Mercken, M., LaFrancois, J., Wang, L., Mathews, P.M., Noble, W., Matsuoka, Y., and Duff, K. (2003). Presenilin redistribution associated with aberrant cholesterol transport enhances β-amyloid production in vivo. J. Neurosci. 23, 5645–5649.
Burns M.P.Vardanian L.Pajoohesh-Ganji A.Wang L.Cooper M.Harris D.C.Duff K.Rebeck G.W.2006. The effects of ABCA1 on cholesterol efflux and Abeta levels in vitro and in vivoJ. Neurochem.98792-800. Burns, M.P., Vardanian, L., Pajoohesh-Ganji, A., Wang, L., Cooper, M., Harris, D.C., Duff, K., and Rebeck, G.W. (2006). The effects of ABCA1 on cholesterol efflux and Abeta levels in vitro and in vivo. J. Neurochem. 98, 792–800.
Chen X.H.Siman R.Iwata A.Meaney D.F.Trojanowski J.Q.Smith D.H.2004. Long-term accumulation of amyloid-beta, beta-secretase, presenilin-1, and caspase-3 in damaged axons following brain traumaAm. J. Pathol.165357-371. Chen, X.H., Siman, R., Iwata, A., Meaney, D.F., Trojanowski, J.Q., and Smith, D.H. (2004). Long-term accumulation of amyloid-beta, beta-secretase, presenilin-1, and caspase-3 in damaged axons following brain trauma. Am. J. Pathol. 165, 357–371.
Ciallella J.R.Ikonomovic M.D.Paljug W.R.Wilbur Y.I.Dixon C.E.Kochanek P.M.Marion D.W.DeKosky S.T.2002. Changes in expression of amyloid precursor protein and interleukin-1beta after experimental traumatic brain injury in ratsJ. Neurotrauma191555-1567. Ciallella, J.R., Ikonomovic, M.D., Paljug, W.R., Wilbur, Y.I., Dixon, C.E., Kochanek, P.M., Marion, D.W., and DeKosky, S.T. (2002). Changes in expression of amyloid precursor protein and interleukin-1beta after experimental traumatic brain injury in rats. J. Neurotrauma 19, 1555–1567.
Combs C.K.Karlo J.C.Kao S.C.Landreth G.E.2001. β-Amyloid stimulation of microglia and monocytes results in TNFα-dependent expression of inducible nitric oxide synthase and neuronal apoptosisJ. Neurosci.211179-1188. Combs, C.K., Karlo, J.C., Kao, S.C., and Landreth, G.E. (2001). β-Amyloid stimulation of microglia and monocytes results in TNFα-dependent expression of inducible nitric oxide synthase and neuronal apoptosis. J. Neurosci. 21, 1179–1188.
Davis-Salinas J.Saporito-Irwin S.M.Cotman C.W.Van Nostrand W.E.1995. Amyloid beta-protein induces its own production in cultured degenerating cerebrovascular smooth muscle cellsJ. Neurochem.65931-934. Davis-Salinas, J., Saporito-Irwin, S.M., Cotman, C.W., and Van Nostrand, W.E. (1995). Amyloid beta-protein induces its own production in cultured degenerating cerebrovascular smooth muscle cells. J. Neurochem. 65, 931–934.
Eckert G.P.Vardanian L.Rebeck G.W.Burns M.P.2007. Regulation of central nervous system cholesterol homeostasis by the liver X receptor agonist TO-901317Neurosci. Lett.42347-52. Eckert, G.P., Vardanian, L., Rebeck, G.W., and Burns, M.P. (2007). Regulation of central nervous system cholesterol homeostasis by the liver X receptor agonist TO-901317. Neurosci. Lett. 423, 47–52.
Faden A.I.Fox G.B.Di X.Knoblach S.M.Cernak I.Mullins P.Nikolaeva M.Kozikowski A.P.2003. Neuroprotective and nootropic actions of a novel cyclized dipeptide after controlled cortical impact injury in miceJ. Cereb. Blood Flow Metab.23355-363. Faden, A.I., Fox, G.B., Di, X., Knoblach, S.M., Cernak, I., Mullins, P., Nikolaeva, M., and Kozikowski, A.P. (2003). Neuroprotective and nootropic actions of a novel cyclized dipeptide after controlled cortical impact injury in mice. J. Cereb. Blood Flow Metab. 23, 355–363.
Fitz N.F.Cronican A.Pham T.Fogg A.Fauq A.H.Chapman R.Lefterov I.Koldamova R.2010. Liver X receptor agonist treatment ameliorates amyloid pathology and memory deficits caused by high-fat diet in APP23 miceJ. Neurosci.306862-6872. Fitz, N.F., Cronican, A., Pham, T., Fogg, A., Fauq, A.H., Chapman, R., Lefterov, I., and Koldamova, R. (2010). Liver X receptor agonist treatment ameliorates amyloid pathology and memory deficits caused by high-fat diet in APP23 mice. J. Neurosci. 30, 6862–6872.
Forloni G.Demicheli F.Giorgi S.Bendotti C.Angeretti N.1992. Expression of amyloid precursor protein mRNAs in endothelial, neuronal and glial cells: modulation by interleukin-1Brain Res. Mol. Brain Res.16128-134. Forloni, G., Demicheli, F., Giorgi, S., Bendotti, C., and Angeretti, N. (1992). Expression of amyloid precursor protein mRNAs in endothelial, neuronal and glial cells: modulation by interleukin-1. Brain Res. Mol. Brain Res. 16, 128–134.
Fraser P.E.Nguyen J.T.Inouye H.Surewicz W.K.Selkoe D.J.Podlisny M.B.Kirschner D.A.1992. Fibril formation by primate, rodent, and Dutch-hemorrhagic analogues of Alzheimer amyloid beta-proteinBiochemistry3110716-10723. Fraser, P.E., Nguyen, J.T., Inouye, H., Surewicz, W.K., Selkoe, D.J., Podlisny, M.B., and Kirschner, D.A. (1992). Fibril formation by primate, rodent, and Dutch-hemorrhagic analogues of Alzheimer amyloid beta-protein. Biochemistry 31, 10716–10723.
Goldgaber D.Harris H.W.Hla T.Maciag T.Donnelly R.J.Jacobsen J.S.Vitek M.P.Gajdusek D.C.1989. Interleukin 1 regulates synthesis of amyloid beta-protein precursor mRNA in human endothelial cellsProc Natl Acad Sci USA867606-7610. Goldgaber, D., Harris, H.W., Hla, T., Maciag, T., Donnelly, R.J., Jacobsen, J.S., Vitek, M.P., and Gajdusek, D.C. (1989). Interleukin 1 regulates synthesis of amyloid beta-protein precursor mRNA in human endothelial cells. Proc Natl Acad Sci USA 86, 7606–7610.
Heyman A.Wilkinson W.E.Stafford J.A.Helms M.J.Sigmon A.H.Weinberg T.1984. Alzheimer's disease: a study of epidemiological aspectsAnn. Neurol.15335-341. Heyman, A., Wilkinson, W.E., Stafford, J.A., Helms, M.J., Sigmon, A.H., and Weinberg, T. (1984). Alzheimer's disease: a study of epidemiological aspects. Ann. Neurol. 15, 335–341.
Hirsch-Reinshagen V.Maia L.F.Burgess B.L.Blain J.F.Naus K.E.McIsaac S.A.Parkinson P.F.Chan J.Y.Tansley G.H.Hayden M.R.Poirier J.Van Nostrand W.Wellington C.L.2005. The absence of ABCA1 decreases soluble ApoE levels but does not diminish amyloid deposition in two murine models of Alzheimer diseaseJ. Biol. Chem.28043243-43256. Hirsch-Reinshagen, V., Maia, L.F., Burgess, B.L., Blain, J.F., Naus, K.E., McIsaac, S.A., Parkinson, P.F., Chan, J.Y., Tansley, G.H., Hayden, M.R., Poirier, J., Van Nostrand, W., and Wellington, C.L. (2005). The absence of ABCA1 decreases soluble ApoE levels but does not diminish amyloid deposition in two murine models of Alzheimer disease. J. Biol. Chem. 280, 43243–43256.
Hoe H.S.Cooper M.J.Burns M.P.Lewis P.A.van der Brug B.M.Chakraborty G.Cartagena C.M.Pak D.T.Cookson M.R.Rebeck G.W.2007. The metalloprotease inhibitor TIMP-3 regulates amyloid precursor protein and apolipoprotein E receptor proteolysisJ. Neurosci.2710895-10905. Hoe, H.S., Cooper, M.J., Burns, M.P., Lewis, P.A., van der Brug, B.M., Chakraborty, G., Cartagena, C.M., Pak, D.T., Cookson, M.R., and Rebeck, G.W. (2007). The metalloprotease inhibitor TIMP-3 regulates amyloid precursor protein and apolipoprotein E receptor proteolysis. J. Neurosci. 27, 10895–10905.
Ikonomovic M.D.Uryu K.Abrahamson E.E.Ciallella J.R.Trojanowski J.Q.Lee V.M.Clark R.S.Marion D.W.Wisniewski S.R.Dekosky S.T.2004. Alzheimer's pathology in human temporal cortex surgically excised after severe brain injuryExp. Neurol.190192-203. Ikonomovic, M.D., Uryu, K., Abrahamson, E.E., Ciallella, J.R., Trojanowski, J.Q., Lee, V.M., Clark, R.S., Marion, D.W., Wisniewski, S.R., and Dekosky, S.T. (2004). Alzheimer's pathology in human temporal cortex surgically excised after severe brain injury. Exp. Neurol. 190, 192–203.
Imaizumi K.Morihara T.Mori Y.Katayama T.Tsuda M.Furuyama T.Wanaka A.Takeda M.Tohyama M.1999. The cell death-promoting gene DP5, which interacts with the BCL2 family, is induced during neuronal apoptosis following exposure to amyloid beta proteinJ. Biol. Chem.2747975-7981. Imaizumi, K., Morihara, T., Mori, Y., Katayama, T., Tsuda, M., Furuyama, T., Wanaka, A., Takeda, M., and Tohyama, M. (1999). The cell death-promoting gene DP5, which interacts with the BCL2 family, is induced during neuronal apoptosis following exposure to amyloid beta protein. J. Biol. Chem. 274, 7975–7981.
Iwata A.Chen X.H.McIntosh T.K.Browne K.D.Smith D.H.2002. Long-term accumulation of amyloid-beta in axons following brain trauma without persistent upregulation of amyloid precursor protein genesJ. Neuropathol. Exp. Neurol.611056-1068. 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.
Jiang Q.Lee C.Y.Mandrekar S.Wilkinson B.Cramer P.Zelcer N.Mann K.Lamb B.Willson T.M.Collins J.L.Richardson J.C.Smith J.D.Comery T.A.Riddell D.Holtzman D.M.Tontonoz P.Landreth G.E.2008. ApoE promotes the proteolytic degradation of AbetaNeuron58681-693. Jiang, Q., Lee, C.Y., Mandrekar, S., Wilkinson, B., Cramer, P., Zelcer, N., Mann, K., Lamb, B., Willson, T.M., Collins, J.L., Richardson, J.C., Smith, J.D., Comery, T.A., Riddell, D., Holtzman, D.M., Tontonoz, P., and Landreth, G.E. (2008). ApoE promotes the proteolytic degradation of Abeta. Neuron 58, 681–693.
Joseph S.B.Castrillo A.Laffitte B.A.Mangelsdorf D.J.Tontonoz P.2003. Reciprocal regulation of inflammation and lipid metabolism by liver X receptorsNat. Med.9213-219. Joseph, S.B., Castrillo, A., Laffitte, B.A., Mangelsdorf, D.J., and Tontonoz, P. (2003). Reciprocal regulation of inflammation and lipid metabolism by liver X receptors. Nat. Med. 9, 213–219.
Kobayashi S.Sasaki T.Katayama T.Hasegawa T.Nagano A.Sato K.2010. Temporal-spatial expression of presenilin 1 and the production of amyloid-beta after acute spinal cord injury in adult ratNeurochem. Int.56387-393. Kobayashi, S., Sasaki, T., Katayama, T., Hasegawa, T., Nagano, A., and Sato, K. (2010). Temporal-spatial expression of presenilin 1 and the production of amyloid-beta after acute spinal cord injury in adult rat. Neurochem. Int. 56, 387–393.
Koldamova R.P.Lefterov I.M.Staufenbiel M.Wolfe D.Huang S.Glorioso J.C.Walter M.Roth M.G.Lazo J.S.2005b. The liver X receptor ligand T0901317 decreases amyloid beta production in vitro and in a mouse model of Alzheimer's diseaseJ. Biol. Chem.2804079-4088. Koldamova, R.P., Lefterov, I.M., Staufenbiel, M., Wolfe, D., Huang, S., Glorioso, J.C., Walter, M., Roth, M.G., and Lazo, J.S. (2005b). The liver X receptor ligand T0901317 decreases amyloid beta production in vitro and in a mouse model of Alzheimer's disease. J. Biol. Chem. 280, 4079–4088.
Koldamova R.Staufenbiel M.Lefterov I.2005a. Lack of ABCA1 considerably decreases brain ApoE level and increases amyloid deposition in APP23 miceJ. Biol. Chem.28043224-43235. Koldamova, R., Staufenbiel, M., and Lefterov, I. (2005a). Lack of ABCA1 considerably decreases brain ApoE level and increases amyloid deposition in APP23 mice. J. Biol. Chem. 280, 43224–43235.
Loane D.J.Pocivavsek A.Moussa C.E.Thompson R.Matsuoka Y.Faden A.I.Rebeck G.W.Burns M.P.2009. Amyloid precursor protein secretases as therapeutic targets for traumatic brain injuryNat. Med.15377-379. Loane, D.J., Pocivavsek, A., Moussa, C.E., Thompson, R., Matsuoka, Y., Faden, A.I., Rebeck, G.W., and Burns, M.P. (2009). Amyloid precursor protein secretases as therapeutic targets for traumatic brain injury. Nat. Med. 15, 377–379.
Mark R.J.Hensley K.Butterfield D.A.Mattson M.P.1995. Amyloid beta-peptide impairs ion-motive ATPase activities: evidence for a role in loss of neuronal Ca2+ homeostasis and cell deathJ. Neurosci.156239-6249. Mark, R.J., Hensley, K., Butterfield, D.A., and Mattson, M.P. (1995). Amyloid beta-peptide impairs ion-motive ATPase activities: evidence for a role in loss of neuronal Ca2+ homeostasis and cell death. J. Neurosci. 15, 6239–6249.
Mattson M.P.Cheng B.Davis D.Bryant K.Lieberburg I.Rydel R.E.1992. β-Amyloid peptides destabilize calcium homeostasis and render human cortical neurons vulnerable to excitotoxicityJ. Neurosci.12376-389. Mattson, M.P., Cheng, B., Davis, D., Bryant, K., Lieberburg, I., and Rydel, R.E. (1992). β-Amyloid peptides destabilize calcium homeostasis and render human cortical neurons vulnerable to excitotoxicity. J. Neurosci. 12, 376–389.
Morales J.R.Ballesteros I.Deniz J.M.Hurtado O.Vivancos J.Nombela F.Lizasoain I.Castrillo A.Moro M.A.2008. Activation of liver X receptors promotes neuroprotection and reduces brain inflammation in experimental strokeCirculation1181450-1459. Morales, J.R., Ballesteros, I., Deniz, J.M., Hurtado, O., Vivancos, J., Nombela, F., Lizasoain, I., Castrillo, A., and Moro, M.A. (2008). Activation of liver X receptors promotes neuroprotection and reduces brain inflammation in experimental stroke. Circulation 118, 1450–1459.
Nadler Y.Alexandrovich A.Grigoriadis N.Hartmann T.Rao K.S.Shohami E.Stein R.2008. Increased expression of the gamma-secretase components presenilin-1 and nicastrin in activated astrocytes and microglia following traumatic brain injuryGlia56552-567. Nadler, Y., Alexandrovich, A., Grigoriadis, N., Hartmann, T., Rao, K.S., Shohami, E., and Stein, R. (2008). Increased expression of the gamma-secretase components presenilin-1 and nicastrin in activated astrocytes and microglia following traumatic brain injury. Glia 56, 552–567.
Nakagawa Y.Nakamura M.McIntosh TK.Rodriguez A.Berlin J.A.Smith D.H.Saatman K.E.Raghupathi R.Clemens J.Saido T.C.Schmidt M.L.Lee V.M.Trojanowski J.Q.1999. Traumatic brain injury in young, amyloid-beta peptide overexpressing transgenic mice induces marked ipsilateral hippocampal atrophy and diminished Abeta deposition during agingJ. Comp. Neurol.411390-398. Nakagawa, Y., Nakamura, M., McIntosh, TK., Rodriguez, A., Berlin, J.A., Smith, D.H., Saatman, K.E., Raghupathi, R., Clemens, J., Saido, T.C., Schmidt, M.L., Lee, V.M., and Trojanowski, J.Q. (1999). Traumatic 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.
Nakagawa Y.Reed L.Nakamura M.McIntosh TK.Smith D.H.Saatman K.E.Raghupathi R.Clemens J.Saido T.C.Lee V.M.Trojanowski J.Q.2000. Brain trauma in aged transgenic mice induces regression of established abeta depositsExp. Neurol.163244-252. Nakagawa, Y., Reed, L., Nakamura, M., McIntosh, TK., Smith, D.H., Saatman, K.E., Raghupathi, R., Clemens, J., Saido, T.C., Lee, V.M., and Trojanowski, J.Q. (2000). Brain trauma in aged transgenic mice induces regression of established abeta deposits. Exp. Neurol. 163, 244–252.
Paterniti I.Genovese T.Mazzon E.Crisafulli C.Di Paola R.Galuppo M.Bramanti P.Cuzzocrea S.2010. Liver X receptor agonist treatment regulates inflammatory response after spinal cord traumaJ. Neurochem.112611-624. Paterniti, I., Genovese, T., Mazzon, E., Crisafulli, C., Di Paola, R., Galuppo, M., Bramanti, P., and Cuzzocrea, S .(2010). Liver X receptor agonist treatment regulates inflammatory response after spinal cord trauma. J. Neurochem. 112, 611–624.
Repa J.J.Li H.Frank-Cannon T.C.Valasek M.A.Turley S.D.Tansey M.G.Dietschy J.M2007. Liver X receptor activation enhances cholesterol loss from the brain, decreases neuroinflammation, and increases survival of the NPC1 mouseJ. Neurosci.2714470-14480. Repa, J.J., Li, H., Frank-Cannon, T.C., Valasek, M.A., Turley, S.D., Tansey, M.G., and Dietschy, J.M (2007). Liver X receptor activation enhances cholesterol loss from the brain, decreases neuroinflammation, and increases survival of the NPC1 mouse. J. Neurosci. 27, 14470–14480.
Roberts G.W.Gentleman S.M.Lynch A.Graham D.I.1991. βA4 amyloid protein deposition in brain after head traumaLancet3381422-1423. 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.
Sironi L.Mitro N.Cimino M.Gelosa P.Guerrini U.Tremoli E.Saez E.2008. Treatment with LXR agonists after focal cerebral ischemia prevents brain damageFEBS Lett.5823396-3400. Sironi, L., Mitro, N., Cimino, M., Gelosa, P., Guerrini, U., Tremoli, E., and Saez, E. (2008). Treatment with LXR agonists after focal cerebral ischemia prevents brain damage. FEBS Lett. 582, 3396–3400.
Smith D.H.Nakamura M.McIntosh T.K.Wang J.Rodriguez A.Chen X.H.Raghupathi R.Saatman K.E.Clemens J.Schmidt M.L.Lee V.M.Trojanowski J.Q.1998. Brain trauma induces massive hippocampal neuron death linked to a surge in beta-amyloid levels in mice overexpressing mutant amyloid precursor proteinAm. J. Pathol.1531005-1010. Smith, D.H., Nakamura, M., McIntosh, T.K., Wang, J., Rodriguez, A., Chen, X.H., Raghupathi, R., Saatman, K.E., Clemens, J., Schmidt, M.L., Lee, V.M., and Trojanowski, J.Q. (1998). Brain 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.
Stone J.R.Okonkwo D.O.Singleton R.H.Mutlu L.K.Helm G.A.Povlishock J.T.2002. Caspase-3-mediated cleavage of amyloid precursor protein and formation of amyloid beta peptide in traumatic axonal injuryJ. Neurotrauma19601-614. Stone, J.R., Okonkwo, D.O., Singleton, R.H., Mutlu, L.K., Helm, G.A., and Povlishock, J.T. (2002). Caspase-3-mediated cleavage of amyloid precursor protein and formation of amyloid beta peptide in traumatic axonal injury. J. Neurotrauma 19, 601–614.
Sun Y.Yao J.Kim T.W.Tall A.R.2003. Expression of liver X receptor target genes decreases cellular amyloid beta peptide secretionJ. Biol. Chem.27827688-27694. Sun, Y., Yao, J., Kim, T.W., and Tall, A.R. (2003). Expression of liver X receptor target genes decreases cellular amyloid beta peptide secretion. J. Biol. Chem. 278, 27688–27694.
Suzuki N.Cheung T.T.Cai X.D.Odaka A.Otvos L. Jr.Eckman C.Golde T.E.Younkin S.G.1994. An increased percentage of long amyloid beta protein secreted by familial amyloid beta protein precursor (beta APP717) mutantsScience2641336-1340. Suzuki, N., Cheung, T.T., Cai, X.D., Odaka, A., Otvos, L., Jr., Eckman, C., Golde, T.E., and Younkin, S.G. (1994). An increased percentage of long amyloid beta protein secreted by familial amyloid beta protein precursor (beta APP717) mutants. Science 264, 1336–1340.
Thomas T.Thomas G.McLendon C.Sutton T.Mullan M.1996. β-Amyloid-mediated vasoactivity and vascular endothelial damageNature380168-171. Thomas, T., Thomas, G., McLendon, C., Sutton, T., and Mullan, M. (1996). β-Amyloid-mediated vasoactivity and vascular endothelial damage. Nature 380, 168–171.
Uryu K.Laurer H.McIntosh T.Pratico D.Martinez D.Leight S.Lee V.M.Trojanowski J.Q.2002. Repetitive mild brain trauma accelerates Abeta deposition, lipid peroxidation, and cognitive impairment in a transgenic mouse model of Alzheimer amyloidosisJ. Neurosci.22446-454. Uryu, K., Laurer, H., McIntosh, T., Pratico, D., Martinez, D., Leight, S., Lee, V.M., and Trojanowski, J.Q. (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.
Wahrle S.E.Jiang H.Parsadanian M.Hartman R.E.Bales K.R.Paul S.M.Holtzman D.M.2005. Deletion of Abca1 increases Aβ deposition in the PDAPP transgenic mouse model of Alzheimer diseaseJ. Biol. Chem.28043236-43242. Wahrle, S.E., Jiang, H., Parsadanian, M., Hartman, R.E., Bales, K.R., Paul, S.M., and Holtzman, D.M. (2005). Deletion of Abca1 increases Aβ deposition in the PDAPP transgenic mouse model of Alzheimer disease. J. Biol. Chem. 280, 43236–43242.
Wahrle S.E.Jiang H.Parsadanian M.Kim J.Li A.Knoten A.Jain S.Hirsch-Reinshagen V.Wellington C.L.Bales K.R.Paul S.M.Holtzman D.M.2008. Overexpression of ABCA1 reduces amyloid deposition in the PDAPP mouse model of Alzheimer diseaseJ. Clin. Invest.118671-682. Wahrle, S.E., Jiang, H., Parsadanian, M., Kim, J., Li, A., Knoten, A., Jain, S., Hirsch-Reinshagen, V., Wellington, C.L., Bales, K.R., Paul, S.M., and Holtzman, D.M. (2008). Overexpression of ABCA1 reduces amyloid deposition in the PDAPP mouse model of Alzheimer disease. J. Clin. Invest. 118, 671–682.
Wang H.Durham L.Dawson H.Song P.Warner D.S.Sullivan P.M.Vitek M.P.Laskowitz D.T.2007. An apolipoprotein E-based therapeutic improves outcome and reduces Alzheimer's disease pathology following closed head injury: evidence of pharmacogenomic interactionNeuroscience1441324-1333. Wang, H., Durham, L., Dawson, H., Song, P., Warner, D.S., Sullivan, P.M., Vitek, M.P., and Laskowitz, D.T. (2007). An apolipoprotein E-based therapeutic improves outcome and reduces Alzheimer's disease pathology following closed head injury: evidence of pharmacogenomic interaction. Neuroscience 144, 1324–1333.
Yamada T.Sasaki H.Furuya H.Miyata T.Goto I.Sakaki Y.1987. Complementary DNA for the mouse homolog of the human amyloid beta protein precursorBiochem. Biophys. Res. Commun.149665-671. Yamada, T., Sasaki, H., Furuya, H., Miyata, T., Goto, I., and Sakaki, Y. (1987). Complementary DNA for the mouse homolog of the human amyloid beta protein precursor. Biochem. Biophys. Res. Commun. 149, 665–671.
Yankner B.A.Dawes L.R.Fisher S.Villa-Komaroff L.Oster-Granite M.L.Neve R.L.1989. Neurotoxicity of a fragment of the amyloid precursor associated with Alzheimer's diseaseScience245417-420. Yankner, B.A., Dawes, L.R., Fisher, S., Villa-Komaroff, L., Oster-Granite, M.L., and Neve, R.L. (1989). Neurotoxicity of a fragment of the amyloid precursor associated with Alzheimer's disease. Science 245, 417–420.
Zelcer N.Khanlou N.Clare R.Jiang Q.Reed-Geaghan E.G.Landreth G.E.Vinters H.V.Tontonoz P.2007. Attenuation of neuroinflammation and Alzheimer's disease pathology by liver X receptorsProc. Natl. Acad. Sci. USA10410601-10606. Zelcer, N., Khanlou, N., Clare, R., Jiang, Q., Reed-Geaghan, E.G., Landreth, G.E., Vinters, H.V., and Tontonoz, P. (2007). Attenuation of neuroinflammation and Alzheimer's disease pathology by liver X receptors. Proc. Natl. Acad. Sci. USA 104, 10601–10606.
Zhang X.Zhou K.Wang R.Cui J.Lipton S.A.Liao F.F.Xu H.Zhang Y.W.2007. Hypoxia-inducible factor 1alpha (HIF-1alpha)-mediated hypoxia increases BACE1 expression and beta-amyloid generationJ. Biol. Chem.28210873-10880. Zhang, X., Zhou, K., Wang, R., Cui, J., Lipton, S.A., Liao, F.F., Xu, H., and Zhang, Y.W. (2007). Hypoxia-inducible factor 1alpha (HIF-1alpha)-mediated hypoxia increases BACE1 expression and beta-amyloid generation. J. Biol. Chem. 282, 10873–10880.

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cover image Journal of Neurotrauma
Journal of Neurotrauma
Volume 28Issue Number 2February 2011
Pages: 225 - 236
PubMed: 21175399

History

Published online: 12 February 2011
Published in print: February 2011
Published ahead of production: 22 December 2010

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David J. Loane
Department of Anesthesiology and Center for Shock Trauma and Anesthesiology Research, National Study Center for Trauma and EMS, University of Maryland School of Medicine, Baltimore, Maryland.
Patricia M. Washington
Department of Neuroscience, Georgetown University Medical Center, Washington, D.C.
Lilit Vardanian
Department of Neuroscience, Georgetown University Medical Center, Washington, D.C.
Ana Pocivavsek
Department of Neuroscience, Georgetown University Medical Center, Washington, D.C.
Hyang-Sook Hoe
Department of Neuroscience, Georgetown University Medical Center, Washington, D.C.
Karen E. Duff
Department of Pathology, Taub Institute for Alzheimer Disease Research, and Integrative Neuroscience New York State Psychiatric Institute, Columbia University Medical Center, New York, New York.
Ibolja Cernak
Johns Hopkins University, Applied Physics Laboratory, Laurel, Maryland.
G. William Rebeck
Department of Neuroscience, Georgetown University Medical Center, Washington, D.C.
Alan I. Faden
Department of Anesthesiology and Center for Shock Trauma and Anesthesiology Research, National Study Center for Trauma and EMS, University of Maryland School of Medicine, Baltimore, Maryland.
Mark P. Burns
Department of Neuroscience, Georgetown University Medical Center, Washington, D.C.

Notes

Address correspondence to:Mark P. Burns, Ph.D.Georgetown University Medical CenterDepartment of NeuroscienceNew Research Building-WP22a3970 Reservoir Road, N.W.Washington, DC 20007E-mail: [email protected]

Author Disclosure Statement

No competing financial interests exist.

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