Neurobiology of Aging
Volume 28, Issue 9 , Pages 1340-1360 , September 2007

Alzheimer’ s disease, oxidative stress and gammahydroxybutyrate

  • Mortimer Mamelak

      Affiliations

    • Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada
    • Baycrest Centre, 3560 Bathurst St., Toronto, Ontario, Canada M6A 2E1
    • Corresponding Author InformationTel.: +1 416 236 5650; fax: +1 416 493 0170.

Received 5 March 2006 ,Revised 14 May 2006 ,Accepted 12 June 2006.

References 

  1. Abe T, Toghi H, Isobe C, Murata T, Sato C. Remarkable increase in the concentration of 8-hydroxyguanosine in cerebrospinal fluid from patients with Alzheimer's disease. Free Radic Biol Med. 2002;70:447–450
  2. Abramov AY, Canevari L, Duchen M. Changes in intracellular calcium and glutathione in astrocytes as the primary mechanism of amyloid neurotoxicity. J Neurosci. 2003;23:5088–5095
  3. Alberts B, Bray D, Lewis J, Raff M, Roberts K, Watson JD. Molecular biology of the cell. 2 ed.. New York and London: Garland Publishing Inc.; 1989;p. 275–340
  4. Armstrong DM, Ikonomovic MD, Sheffield R, Wenthold RJ. AMPA-selective glutamate receptor subtype immunoreactivity in the entorhinal cortex of non-demented elderly and patients with Alzheimer's disease.. Brain Res. 1994;639:207–216
  5. Atwood CS, Huang X, Moir RD, Tanzi RE, Bush AI. Role of free radicals and metal ions in the pathogenesis of Alzheimer's disease. In:  Sigel A,  Sigel H editor. Metals in biological systems. 36 ed.. New York: Marcel Dekker; 1999;p. 309–364
  6. Atwood CS, Obrenovich ME, Liu T, Chan H, Perry G, Smith MA, et al. Amyloid-β: a chameleon walking in two worlds: a review of the trophic and toxic properties of amyloid-β. Brain Res Rev. 2003;43:1–16
  7. Balazs L, Leon M. Evidence of an oxidative challenge in the Alzheimer's brain. Neurochem Res. 1994;19:1131–1137
  8. Banerjee PK, Snead OC. Presynaptic gammahydroxybutyric acid (GHB) and gammaaminobutyric acid (GABAB) receptor mediated relaease of GABA and glutamate (GLU) in rat thalamic ventrobasal nucleus (VB): a possible mechanism for the generation of absence like seizures induced by GHB. J Pharmacol Exp Ther. 1995;273:1573–1643
  9. Berlett BS, Stadtman ER. Protein oxidation in aging, disease and oxidative stress. J Biol Chem. 1997;272:20313–20316
  10. Bernasconi R, Mathivet P, Otten V, Bettler B, Bischoff S, Marescaux C. Part of the pharmacological actions of gammahydroxybutyrate are mediated by GABAB receptors. In:  Tunnicliff G,  Cash CD editor. Gammahydroxybutyrate: molecular. Functional and Clinical Aspects. New York: Taylor and Francis; 2002;p. 28–63
  11. Bishop GM, Robinson SR. Deposits of fibrillar Aβ do not cause neuronal loss or ferritin expression in adult rat brain. J Neural Transm. 2003;110:381–400
  12. Bishop GM, Robinson SR. Human Aβ1−42 reduces iron-induced toxicity in rat cerebral cortex. J Neurosci Res. 2003;73:16–23
  13. Blanc EM, Keller JN, Fernandez S, Mattson MP. 4-Hydroxynonenal, a lipid peroxidation product, impairs glutamate transport in cortical astrocytes. GLIA. 1998;22:149–160
  14. Boerwinkle E, Sing CF. The use of measured genotype information in the analysis of quantitative phenotypes in man. Ann Human Genet. 1987;61:211–226
  15. Bowling AC, Mutisya EM, Walker LC, Price DL, Cork LC, Beal MF. Age-dependent impairment of mitochondrial function in primate brain. J Neurochem. 1993;60:1964–1967
  16. Boyd AJ, Sherman IA, Saibil FG, Mamelak M. The protective effect of γ-hydroxybutyrate in regional intestinal ischemia in the hamster. Gastroenterology. 1990;99:860–862
  17. Boyd AJ, Sherman IA, Saibil FG. Intestinal microcirculation and leukocyte behavior in ischemia-reperfusion injury. Microvasc Res. 1994;47:355–368
  18. Braak E, Braak H, Mendelkow E-M. A sequence of cytoskeletal changes related to the formation of neurofibrillary tangles and neuropil threads. Acta Neuropathol. 1994;87:554–567
  19. Braak H, Braak E. Staging of Alzheimer's disease-related neurofibrillary changes. Neurobiol Aging. 1995;16:271–284
  20. Bruno V, Battaglia G, Copani A, D’Onofrio M, Di Iorio P, De Blasi A, et al. Metabotropic glutamate receptor subtypes as targets for neuroprotective drugs. J Cereb Blood Flow Metab. 2001;21:1013–1033
  21. Bush AI. The metallobiology of Alzheimer's disease. Trends Neurosci. 2003;26:207–214
  22. Butterfield DA, Lauderback CM. Lipid peroxidation and protein oxidation in Alzheimer's disease brain: potential causes and consequences involving amyloid β-peptide-associated free radical oxidative stress. Free Radic Biol Med. 2002;32:1050–1060
  23. Butterfield DA. Amyloid β-peptide (1–42)-induced oxidative stress and neurotoxicity: implications for neurodegeneration in Alzheimer's disease brain. A review. Free Radic Res. 2002;36:1307–1313
  24. Butterfield DA, Pocernich CB. The glutamatergic system and Alzheimer's disease. CNS Drugs. 2003;17:641–652
  25. Buysse DJ, Browman KE, Monk TH, Reynolds CFI, Fasiczka AL, Kupfer DJ. Napping and 24-h sleep/wake patterns in healthy elderly and young adults. J Am Geriatric Soc. 1992;40:779–786
  26. Buzadžiæ B, Spasiæ M, Saièiæ ZS, Radojièiæ R, Petroviæ VM, Halliwell B. Antioxidant defenses in the ground squirrel citellus citellus. 2. The effect of hibernation. Free Radic Biol Med. 1990;9:407–413
  27. Calver AR, Medhurst AD, Robbin MJ, Charles KJ, Evans ML, Harrison DC, et al. The expression of GABAB, and GABAB2 receptor subunits in the CNS differs from that in peripheral tissues. Neuroscience. 2000;100:155–170
  28. Capsoni S, Ugolini G, Comparini A, Ruberti F, Berardi N, Cattaneo A. Alzheimer-like neurodegeneration in aged antinerve growth factor transgenic mice. PNAS. 2000;97:6826–6831
  29. Carai MAM, Colombo G, Brunetti G, Melis S, Serra S, Vacca G, et al. Role of GABAB receptors in the sedative/hypnotic effect of γ-hydroxybutyric acid. Eur J Pharmacol. 2001;428:315–321
  30. Carpenter M, Crutcher K, Kater S. An analysis of the effects of Alzheimer's plaques on living neurons. Neurobiol Aging. 1993;14:207–215
  31. Cash AD, Aliev G, Siedlak SL, Nunomura A, Fujioka H, Zhu X, et al. Microtubule reduction in Alzheimer's disease and aging is independent of τ filament formation. Am J Pathol. 2003;162:1623–1627
  32. Cash CD, Tunnicliff G. The gammahydroxybutyrate receptor in the brain. In:  Tunnicliff G,  Cash CD editor. Gammahydroxybutyrate: molecular, functional and clinical aspects. New York: Taylor and Francis; 2002;p. 17–27
  33. Castellani RJ, Hirai K, Aliev G, Drew KL, Nunomura A, Takeda A, et al. Role of mitochondrial dysfunction in Alzheimer's disease. J Neurosci Res. 2002;70:357–360
  34. Chan C-W, Dharmarajan A, Atwood CS, Huang X, Tanzi RE, Bush AI, et al. Antiapoptotic action of Alzheimer Aβ. Alzheimer's Rep. 1999;2:1–6
  35. Chandrasekaran K, Hatanpaa K, Brady DR, Rapoport S. Evidence for physiological down regulation of brain oxidative phosphorylation in Alzheimer's disease. Exp Neurol. 1996;142:80–88
  36. Chen G-J, Xu J, Lahousse SA, Caggiano NL, de la Monte SM. Transient hypoxia causes Alzheimer-type molecular and biochemical abnormalities in cortical neurons: potential strategies for neuroprotection. J Alzheimer's Dis. 2003;5:209–228
  37. Cherny RA, Legg JT, McLean CA, Fairlie DP, Huang X, Atwood CS, et al. Aqueous dissolution of Alzheimer's disease Aβ amyloid deposits by biometal depletion. J Biol Chem. 1999;274:23223–23228
  38. Coleman PD, Yao PJ. Synaptic slaughter in Alzheimer's disease. Neurobiol Aging. 2003;24:1023–1027
  39. Coleman PD, Federoff H, Kurlan R. A focus on the synapse for neuroprotection in Alzheimer disease and other dementias. Neurology. 2004;63:1155–1162
  40. Coyle J, Puttfarcken P. Oxidative stress, glutamate, and neurodegenerative disorders. Science. 1993;262:689–700
  41. Crunelli V, Leresche N. Action of gammahydroxybutyrate on neuronal excitability and underlying membrane conductances. In:  Tunnicliff G,  Cash CD editor. Gammahydroxybutyrate: molecular, functional and clinical aspects. New York: Taylor and Francis; 2002;p. 75–110
  42. Cuajungco MP, Fagét KY, Huang X, Tanzi RE, Bush AI. Metal chelation as a potential therapy for Alzheimer's disease. Ann NY Acad Sci. 2000;920:292–304
  43. De Jong GI, De Vos RA, Jansen Steur EN, Luiten PGM. Cerebrovascular hypoperfusion: a risk factor for Alzheimer's disease? Animal Model and Postmortem Human Studies. Ann NY Acad Sci. 1997;826:56–74
  44. de la Torre JC, Stefano GB. Evidence that Alzheimer's disease is a microvascular disorder: the role of constitutive nitric oxide. Brain Res Rev. 2000;34:119–136
  45. de la Torre JC. Critically attained threshold of cerebral hypoperfusion: the CATCH hypothesis of Alzheimer's pathogenesis. Neurobiol Aging. 2000;21:331–342
  46. de la Torre JC. Vascular basis of Alzheimer's pathogenesis. Ann NY Acad Sci. 2002;977:196–215
  47. Diez M, Koistinaho J, Kahn K, Games D, Hokfelt T. Neuropeptides in hippocampus and cortex of transgenic mice over expressing V717F β-amyloid precursor protein-initial observation. Neuroscience. 2000;100:259–286
  48. Doležal V, Kašparová J. β-amyloid and cholinergic neurons. Neurochem Res. 2003;28:499–506
  49. Dringen R. Metabolism and functions of glutathione in brain. Prog Neurobiol. 2000;62:649–671
  50. Elsasser A, Schlepper M, Klovekorn W-P, Cai W, Zimmermann R, Muller K-D, et al. Hibernating myocardium: an incomplete adaptation to ischemia. Circulation. 1997;96:2920–2931
  51. Escuret E, Roquefeuil B, Frerebeau P, Baldy-Moulinier M. Effect of hyperventilation associated with administration of central nervous depressants in brain injuries. Acta Neurol Scand Suppl. 1977;64:154–155
  52. Ferraguli F, Baldani-Guerra B, Corse M, Nakanishi S, Corti C. Activation of the extracellular signal regulated kinase 2 by metabotropic glutamate receptors. Eur J Neurosci. 1999;11:2073
  53. Ferraro L, Tanganelli S, O’Connor WT, Francesconi W, Loche A, Gessa GL, et al. γ-Hydroxybutyrate modulation of glutamate levels in the hippocampus: an in vivo and in vitro study. J Neurochem. 2001;78:929–939
  54. Finkel T, Holbrook NJ. Oxidants, oxidative stress and the biology of ageing. Nature. 2000;408:239–247
  55. Frears ER, Stephens DJ, Walters CE, Davies H, Austen BM. The role of cholesterol in the biosynthesis of β-amyloid. Neuroreport. 1999;10:1699–1705
  56. Freeman BA, Crapo JD. Biology of disease: free radicals and tissue injury. Lab Invest. 1982;47:412–442
  57. Frerichs KU, Kennedy C, Sokoloff L, Hallenbeck JM. Local cerebral blood flow during hibernation, a model of natural tolerance to “cerebral ischemia”. J Cereb Blood Flow Metab. 1994;14:193–205
  58. Gabbita SP, Lovell MA, Markesbery WR. Increased nuclear DNA oxidation in the brain in Alzheimer's disease. J Neurochem. 1998;71:2034–2040
  59. Gabuzda D, Busciglio J, Chen LB, Matsudaira P, Yankner BA. Inhibition of energy metabolism alters the processing of amyloid precursor protein and induces a potentially amyloidogenic derivative. J Biol Chem. 1994;269:13623–13628
  60. Ghebremedhin E, Schultz C, Braak E, Braak H. High frequency of apolipoprotein E∈4 allele in young individuals with very mild Alzheimer's disease related neurofibrillary tangles. Exp Neurol. 1998;153:152–155
  61. Godon C, Lagniel G, Lee J, Buhler J-M, Kieffer S, Perrot M, et al. The H2O2 stimulon in Saccharomyces cerevisiae. J Biol Chem. 1998;273:22480–22489
  62. Gómez-Isla T, Hollister R, West H, Mui S, Growdon JH, Petersen RC, et al. Neuronal loss correlates with but exceeds neurofibrillary tangles in Alzheimer's disease. Ann Neurol. 1997;41:17–24
  63. Haller C, Mende M, Schuier F, Schuh R, Schröck H, Kuschinsky W. Effect of gammahydroxybutyrate on local and global glucose metabolism in the anaesthetized cat brain. J Cereb Blood Flow Metab. 1990;10:493–498
  64. Halliwell B. Reactive oxygen species and the central nervous system. J Neurochem. 1992;59:1609–1623
  65. Hamel E. Cholinergic modulation of the cortical microvascular bed. Prog Brain Res. 2004;145:171–178
  66. Hattori N, Kitagawa K, Higashida T, Yagyu K, Shimohama S, Wataya T, et al. CI-ATPase and Na+/K+-ATPase activities in Alzheimer's disease brains. Neurosci Lett. 1998;254:141–144
  67. Heininger K. A unifying hypothesis of Alzheimer's disease. IV. Causation and sequence of events. Rev Neurosci. 2000;11:213–328
  68. Heller HC, Krilowicz BL, Kilduff TS. Neural mechanisms controlling hibernation living in the cold. INSERM/John Libbey Eurotext Ltd.; 1989;p. 447–59
  69. Hellweg R, Nitsch R, Hock C, Jaksch M, Hoyer S. Nerve growth factor and choline acetyltransferase activity levels in the rat brain following experimental impairment of cerebral glucose and energy metabolism. J Neurosci Res. 1992;31:479–486
  70. Hirai K, Aliev G, Nunomura A, Fujioka H, Russell RL, Atwood CS, et al. Mitochondrial abnormalities in Alzheimer's disease. J Neurosci. 2001;21:3017–3023
  71. Hof PR, Morrison JH. The cellular basis of cortical disconnection in Alzheimer disease and related dementing conditions. In:  Terry RD,  Katzman R,  Bick KL,  Sisodia SS editor. Alzheimer disease. 2 ed.. Philadelphia: Lippincott, Williams and Wilkins; 1999;p. 207–232
  72. Hoshi M, Takashima A, Murayama M, Yasutake K, Yoshida N, Ishiguro K, et al. Nontoxic amyloid β peptide 1−42 suppresses acetylcholine synthesis. J Biol Chem. 1997;272:2038–2041
  73. Hoyer S. Brain oxidative energy and related metabolism, neuronal stress, and Alzheimer's disease: a speculative synthesis. J Geriatric Psychiatry Neurol. 1993;6:3–13
  74. Hu RQ, Banerjee PK, Snead OC. Regulation of gammaaminobutyric acid (GABA) release in cerebral cortex in the gammahydroxybutyric acid model of absence seizures in rat. Neuropharmacology. 2000;39:427–439
  75. Huang X, Atwood CS, Hartshorn MA, Multhaup G, Goldstein LE, Scarpa RC, et al. The Aβ peptide of Alzheimer's disease directly produces hydrogen peroxide through metal ion reduction. Biochemistry. 1999;38:7609–7616
  76. Hyslop PA, Hinshaw DB, Halsey WAJr , Schraufstätter IU, Sauerheber RD, Spragg RG, et al. Mechanisms of oxidant-mediated cell injury. J Biol Chem. 1988;263:1665–1675
  77. Igbavboa U, Avdulov NA, Chochina SV, Wood WG. Transbilayer distribution of cholesterol is modified in brain synaptic plasma membranes of knockout mice deficient in the low-density lipoprotein receptor, apolipoprotein E, or both proteins. J Neurochem. 1997;69:1661–1667
  78. Ikeda M, Ikeda-Sagara M, Okada T, Clement P, Urade Y, Nagai T, et al. Brain oxidation is an initial process in sleep induction. Neuroscience. 2005;130:1029–1040
  79. Ikeyama S, Kokkonen G, Shack S, Wang X-T, Holdbrook NJ. Loss in oxidative stress tolerance with aging linked to reduced extracellular signal-regulated kinase and Akt kinase activities. FASEB J. 2002;16:114–116
  80. Ikonomovic MD, Armstrong DM. Distribtuion of AMPA receptor subunits in the nucleus basalis of Meynart in aged humans: implications for selective neuronal degeneration. Brain Res. 1996;716:229–232
  81. Ikonomovic MD, Mizukami K, Davies P, Hamilton R, Sheffield R, Armstrong DM. The loss of GluR2(3) immunoreactivity precedes neurofibrillary tangle formation in the entorhinal cortex and hippocampus of Alzheimer brains. J Neuropathol Exp Neurol. 1997;56:1018–1027
  82. Ingelsson M, Fukumoto H, Newell KL, Growdon JH, Hedley-Whyte ET, Frosch MP, et al. Early Aβ accumulation and progressive synaptic loss, gliosis, and tangle formation in AD brain. Neurology. 2004;62:925–931
  83. Isacson O, Seo H, Lin L, Albeck D, Granholm A-C. Alzheimer's disease and Down's syndrome: roles of APP, trophic factors and ACh. Trends Neurosci. 2002;25:79–82
  84. Jaffar S, Counts SE, Ma SY, Dadko E, Gorodn MN, Morgan D, et al. Neuropathology of mice carrying mutant APPswe and or PS1M14GL transgene alterations in the p75NTR cholinergic basal forebrain septo hippocampal pathway. Exp Neurol. 2001;170:227–243
  85. Jagust W, Thisted R, Devous M, Van Heertum R, Mayberg H, Jobst K, et al. SPECT perfusion imaging in the diagnosis of Alzheimer's disease: a clinical-pathologic study. Neurology. 2001;56:950–956
  86. Jarvik GP, Wijsman EM, Kukull WA, Schellenberg G, Yu C, Larson EB. Interactions of apoliprotein E genotype, total cholesterol level, age, and sex in prediction of Alzheimer's disease: a case control study. Neurology. 1995;45:1092–1096
  87. Jensen K, Mody I. GHB depresses fast excitatory and inhibitory synaptic transmission via GABAB receptors in mouse neocortical neurons. Cereb Cortex. 2001;11:424–429
  88. Ježek P, Žácková M, Ružicka M, Škobisová E, Jaburek M. Mitochondrial uncoupling proteins-facts and fantasies. Physiol Res. 2004;53:S199–S211
  89. Kaibara T, Sutherland GR, Colbourne F, Tyson RL. Hypothermia: depression of tricarboxylic acid cycle flux and evidence for pentose phosphate shunt upregulation. J Neurosurg. 1999;90:339–347
  90. Kalaria RN, Ballard C. Overlap between pathology of Alzheimer disease and vascular dementia. Alzheimer Dis Assoc Disorders. 1999;13(Suppl 3):S115–S123
  91. Kalinchuk AV, Urrila A-S, Alanko L, Heiskanen S, Wigren H-K, Suomela M, et al. Local energy depletion in the basal forebrain increases sleep. Eur J Neurosci. 2003;17:863–869
  92. Kaufman EE. Metabolism and distribution of gamma hydroxybutyrate in the brain. In:  Tunnicliff G,  Cash CD editor. Gammahydroxybutyrate: molecular, functional and clinical aspects. New York: Taylor and Francis; 2002;p. 1–6
  93. Kaufman EE, Porrino LJ, Nelson T. Pyretic action of low doses of γ-hydroxybutyrate in rats. Biochem Pharmacol. 1990;40:2637–2640
  94. Kaufman EE, Nelson T. An overview of γ-hydroxybutyrate catabolism: the role of the cytosolic NADP+ dependent oxidoreductase EC 1.1.1.19 and of a mitochondrial hydroxyacid–oxoacid transhydrogenase in the initial, rate-limiting step in this pathway. Neurochem Res. 1991;16:965–974
  95. Kaupmann K, Cryan JF, Wellendorph P, Mombereau C, Sansig G, Klebs K, et al. Specific γ-hydroxybutyrate-binding sites but loss of pharmacological effects of γ-hydroxybutyrate in GABAB(1)-deficient mice. Eur J Neurosci. 2003;18:2722–2730
  96. Keller JN, Mark RJ, Bruce AJ, Blanc EM, Rothstein JD, Uchida K, et al. 4-Hydroxynonenal, an aldehydic product of membrane lipid peroxidation, impaires glutamate transport and mitochondrial function in synaptosomes. Neuroscience. 1997;80:685–696
  97. Keller JN, Schmitt FA, Scheff SW, Ding Q, Chen Q, Butterfield DA, et al. Evidence of increased oxidative damage in subjects with mild cognitive impairment. Neurology. 2005;64:1152–1156
  98. Kemmel V, Taleb O, Perard A, Andrianmampandry C, Siffert JC, Mark RJ, et al. Neurochemical and electrophysiological evidence for the existence of a functional gammahydroxybutyrate system in NCB-20 neurons. Neuroscience. 1998;86:989–1000
  99. Kesslak J, Yuan D, Neeper S, Cotman CW. Vulnerability of the hippocampus to kainate excitotoxicity. Neurosci Lett. 1995;188:117–120
  100. Kogure D, Matsuda H, Ohnishi T, Asada T, Uno M, Kunihiro T. Longitudinal evaluation of early Alzheimer's disease using brain perfusion SPECT. J Nucl Med. 2000;41:1145–1162
  101. Kolin A, Brezina A, Mamelak M. Cardioprotective effects of sodium gamma-hydroxybutyrate (GHB) on brain induced myocardial injury. In vivo. 1991;5:429–432
  102. Koo E, Park L, Selkoe DJ. Amyloid-beta protein as a substrate interacts with extravellular matrix to promote neurite outgrowth. PNAS. 1993;90:4748–4752
  103. Kril JJ, Patel S, Harding AJ, Halliday GM. Neuron loss from the hippocampus of Alzheimer's disease exceeds extracellular neurofibrillary tangle formation. Acta Neuropathol. 2002;103:370–376
  104. Kulinskii V, Klimova A. The radioprotective effect of GABA-tropic substance. Radiobiologiia. 1993;33:133–136
  105. Kuschinsky W, Suda S, Sokoloff L. Influence of the gamma-hydroxybutyrate on the relationship between local cerebral glucose utilization and local cerebral blood flow in the rat brain. J Cereb Blood Flow Metab. 1985;5:58–64
  106. Laborit H. Sodium 4-hydroxybutyrate. Int J Neuropharmacol. 1964;3:433–452
  107. Lauderback CM, Hackett JM, Huang FF, Keller JN, Szweda LI, Markesbery WR, et al. The glial glutamate transporter, GLT-1, is oxidatively modified by 4-hydroxy-2-nonenal in the Alzheimer's disease brain: the role of Aβ1–42. J Neurochem. 2001;78:413–416
  108. Lauderback CM, Kanski J, Hackett JM, Maeda N, Kindy MS, Butterfield DA. Apolipoprotein E modulates Alzheimer's Aβ (1–42)-induced oxidative damage to synaptosomes in an allele-specific manner. Brain Res. 2002;924:90–97
  109. Lavyne MH, Hairiri RJ, Tankosic T, Babiak T. Effect of low dose γ-butyrolactone therapy on forebrain neuronal ischemia in the unrestrained, awake rat. Neurosurgery. 1983;12:430–434
  110. Lee H, Ogawa O, Zhu X, O’Neill MJ, Petersen RB, Castellani RJ, et al. Aberrant expression of metabotropic glutamate receptor 2 in the vulnerable neurons of Alzheimer's disease. Acta Neuropathol. 2004;107:365–371
  111. Lee H, Moreira PI, Zhu X, Smith MA, Perry G. Staying connected; synapses in Alzheimer disease. Am J Pathol. 2004;165(5):1461–1464
  112. Lin MT, Chern YF, Wang HS, Chandra A. Effects of γ-hydroxybutyric acid on metabolic, respiratory and vasomotor activities and body temperature in rats. J Pharmacol Exp Therap. 1979;211:167–170
  113. Loo DT, Copani A, Pike CJ, Whittemore ER, Walencewicz AJ, Cotman CW. Apoptosis is induced by β-amylod in cultured central nervous system neurons. Neurobiology. 1993;90:7951–7955
  114. Lopatin AF, Riabtseva EG, Riabova VV, Lipatova TI. Effect of sodium oxybutyrate on metabolic indices. Farmakologiia I Toksikologiia. 1984;47:53–55
  115. Lovell MA, Robertson JD, Teesdale WJ, Campbell JL, Markesbery WR. Copper, iron and zinc in Alzheimer's disease senile plaques. J Neurol Sci. 1998;158:47–52
  116. Lovell MA, Xie C, Markesbery WR. Acrolein, a product of lipid peroxidation, inhibits glucose and glutamate uptake in primary neuronal cultures. Free Radic Biol Med. 2000;29:714–720
  117. Lovell MA, Xie C, Markesbery WR. Acrolein is increased in Alzheimer's disease brain and is toxic to primary hippocampal cultures. Neurobiol Aging. 2001;22:187–194
  118. Lue L-F, Kuo Y-M, Roher AE, Brachova L, Shen Y, Sue L, et al. Soluble amyloid β peptide concentration as a predictor of synaptic change in Alzheimer's disease. Am J Pathol. 1999;155:853–862
  119. MacMillan V. The effects of gamma-hydroxybutyrate and gamma-butyrolactone upon the energy metabolism of the normoxic and hypoxic rat brain. Brain Res. 1978;146:177–187
  120. Madden TE, Johnson SW. Gammahydroxybutyrate is a GABAB receptor agonist that increases a potassium conductance in rat ventral tegmental dopamine neurons. J Pharmacol Exp Therap. 1998;287:261–265
  121. Madsen PL, Schmidt JF, Wildschiodtz G, Friberg L, Holm S, Vorstrup S, et al. Cerebral O2 metabolism and cerebral blood flow in humans during deep and rapid-eye-movement sleep. J Appl Physiol. 1985;70:2597–2601
  122. Madsen PL, Schmidt JF, Holm S, Vorstrup S, Lassen NA, Wildschiodtz G. Cerebral oxygen metabolism and cerebral blood flow in man during light sleep (stage 2). Brain Res. 1991;557:217–220
  123. Mamelak M. Gammahydroxybutyrate: An endogenous regulator of energy metabolism. Neurosci Biobehav Rev. 1989;13:187–198
  124. Mamelak M, Hyndman D. Gammahydroxybutyrate and oxidative stress. In:  Tunnicliff G,  Cash CD editor. Gammahydroxybutyrate: molecular, functional and clinical aspects. New York: Taylor and Francis; 2002;p. 218–235
  125. Mamelak M, Black J, Montplaisir J, Ristanovic R. A pilot study on the effects of sodium oxybate on sleep architecture and daytime alertness in narcolepsy. Sleep. 2004;27:1–8
  126. Mandelkow E-M, Stamer K, Vogel R, Thies E, Mandelkow E. Clogging of axons by tau, inhibition of axonal traffic and starvation of synapses. Neurobiol Aging. 2003;24:1079–1085
  127. Maquet P, Dive D, Salmon E, Sadzot B, Franco G, Poirrier R, et al. Cerebral glucose utilization during sleep-wake cycle in man determined by positron emission tomography and [18F]2-fluoro-2-deoxy-d-glucose method. Brain Res. 1990;513:136–143
  128. Maquet P, Dive D, Salmon E, Sadzot B, Franco G, Poirrier R, et al. Cerebral glucose utilization during stage 2 sleep in man. Brain Res. 1992;571:149–153
  129. Mark RJ, Hensley KM, Butterfield DA, Mattson MP. Amyloid β-peptide impairs ion-motive ATPase activities: evidence for a role in loss of neuronal Ca+ homeostasis and cell death. J Neurosci. 1995;15:6239–6249
  130. Mark RJ, Lovell MA, Markesbery WR, Uchida K, Mattson MP. A role for 4-hydroxynonenal, an aldehydic product of lipid peroxidation, in disruption of ion homeostasis and neuronal death induced by amyloid beta peptide. J Neurochem. 1997;68:255–264
  131. Mark RJ, Pang Z, Geddes JW, Uchida K, Mattson MP. Amyloid β peptide impairs glucose transport in hippocampal and cortical neurons; involvement of membrane lipid peroxidation. J Neurosci. 1997;17:1046–1054
  132. Markesbery WR, Lovell MA. Four-hydroxynonenal, a product of lipid peroxidation, is increased in the brain in Alzheimer's disease. Neurobiol Aging. 1998;19:33–36
  133. Markesbery WR, Ehmann WD. Oxidative stress in Alzheimer disease. In:  Terry RD,  Katzman R,  Bick KL,  Sisodia SS editor. Alzheimer disease. 2 ed.. Philadelphia: Lippincott, Williams and Wilkins; 1999;p. 401–414
  134. Martins RN, Harper CG, Stokes GB, Masters CL. Increased cerebral glucose-6-phosphate dehydrogenase activity in Alzheimer's disease may reflect oxidative stress. J Neurochem. 1986;46:1042–1045
  135. Masliah E, Terry RD, Alford M, DeTeresa R, Hansen L. Cortical and subcortical patterns of synaptophysinlike immunoreactivity in Alzheimer's disease. Am J Pathol. 1991;138:235–246
  136. Masliah E, Ellisman M, Carragher B, Mallory M, Young S, Hansen L, et al. Three-dimensional analysis of the relationship between synaptic pathology and neuropil threads in Alzheimer disease. J Neuropathol Exp Neurol. 1992;51:404–414
  137. Mattson MP, Lovell MA, Furukawa K, Markesbery WR. Neurotrophis factors attenuate glutamate-induced accumulation of peroxides, elevation of [Ca2+] and neurotoxicity and increase antioxidant enzyme activities in hippocampal neurons. J Neurochem. 1995;65:1740–1754
  138. Mattson MP, Fu W, Waeg G, Uchida K. 4 Hydroxynonenal, a product of lipid peroxidation, inhibits dephosphorylation of the microtubule-associated protein tau. Neuroreport. 1997;8:2275–2281
  139. McCarron RM, Sieckmann DG, Yu EZ, Frerichs KU, Hallenbeck JM. Hibernation, a state of natural tolerance to profound reduction in organ blood flow and oxygen delivery capcity. In:  Storey KB editors. Molecular mechanisms of metabolic arrest: life in limbo. Bios Scientific Publishers Limited; 2001;p. 23–42
  140. Mecocci P, MacGarvery U, Kaufman AE, Koontz D, Shoffner JM, Wallace DC, et al. Oxidative damage to mitochondrial DNA shows marked age-dependent increased in human brain. Ann Neurol. 1993;34:609–616
  141. Meerson FZ, Kagan VE, Prilipko LL, Rozhitskaya II. The failing heart: adaptation and deadaptation. New York: Raven Press; 1983;p. 67–127
  142. Meguro K, Blaizot X, Kondoh Y, Le Mestric C, Baron JC, Chavoic C. Neocortical and hippocampal glucose hypometabolism following neurotoxic lesions of the entorhinal and peripheral cortices in the non human primate as shown by PET. Implications for Alzheimer's disease. Brain. 1999;122:1519–1531
  143. Minoshima S, Cross DJ, Foster NL, Henry TR, Kuhl DE. Discordance between traditional pathologic and energy metabolic changes in very early Alzheimer's disease. Ann NY Acad Sci. 2000;893:350–352
  144. Miyata M, Smith JD. Apolipoprotein E allele-specific antioxidant activity and effects on cyotoxicity by oxidative insults and β-amyloid peptides. Nat Genet. 1996;14:55–61
  145. Montine KS, Olson SJ, Ventkatamaran A, Wetsell WO, Graham DG, Montine TJ. Immunohistochemical detection of 4-hydroxy-2-nonenal adducts in Alzheimer disease is associated with inheritance of APOE4. Am J Pathol. 1997;150:437–443
  146. Montine KS, Reich E, Neely MD, Sidell KR, Olson SJ, Markesbery WR, et al. Distribution of reducible 4-hydroxynonenal adduct immunoreactivity in Alzheimer disease is associated with APOE genotype. J Neuropathol Exp Neurol. 1998;57:415–425
  147. Montine TJ, Beal MF, Cudkowicz ME, O’Donnell H, Margolin RA, McFarland L, et al. Increased CSF F2-isoprostane concentration in probable AD. Neurology. 1999;52:562–565
  148. Morrison JH, Hof PR. Selective vulnerability of corticocortical and hippocampal circuits in aging and Alzheimer's disease. Prog Brain Res. 2002;136:467–486
  149. Morsch R, Simon W, Coleman PD. Neurons may live for decades with neurofibrillary tangles. J Neuropathol Exp Neurol. 1999;58:188–197
  150. Murray KR, Granner DK, Mayes PA, Rodwell VW. Harper's Illustrated Biochemistry. 26 ed.. New York: Lange Medical Book/McGraw-Hill; 2003;
  151. Näslund J, Haroutunian V, Mohs R, Davis KL, Davies P, Greengard P, et al. Correlation between elevated levels of amyloid β-peptide in the brain and cognitive decline. JAMA. 2000;283:1571–1577
  152. Neely MD, Sidell KR, Graham DG, Montine TJ. The Lipid peroxidation product 4-hydroxynonenal inhibits neurite outgrowth, disrupts neuronal microtubules, and modifies cellural tubulin. J Neurochem. 1999;72:2323–2333
  153. Nelson T, Kaufman EE, Kline J, Sokoloff L. The extraneural distribution of γ-hydroxybutyrate. J Neurochem. 1981;37:1345–1348
  154. Notkola I, Sulkava R, Pekkanen J, Erkinjuntti T, Ehnholm C, Kivinen P, et al. Serum total cholesterol, apolipoprotein E epsilon 4 allele, and Alzheimer's disease. Neuroepidemiology. 1998;17:17–20
  155. Nunomura A, Perry G, Pappolla MA, Wade R, Hirai K, Chiba S, et al. RNA oxidation is a prominent feature of vulnerable neurons in Alzheimer's disease. J Neurosci. 1999;19:1959–1964
  156. Nunomura A, Perry G, Pappolla MA, Friedland RP, Hirai K, Chiba S, et al. Neuronal oxidative stress precedes amyloid-β deposition in down syndrome. J Neuropathol Exp Neurol. 2000;59:1011–1017
  157. Nunomura A, Perry G, Aliev G, Hirai K, Takeda A, Balraj EK, et al. Oxidative damage is the earliest event in Alzheimer disease. J Neuropathol Exp Neurol. 2001;60:759–767
  158. Ottani A, Saltini S, Bartiromo M, Zaffe D, Botticelli AR, Ferrari A, et al. Effect of γ-hydroxybutyrate in two rat models of focal cerebral damage. Brain Res. 2003;986:181–190
  159. Paola D, Domenicotti C, Nitti M, Vitali A, Borghi R, Cottalasso D, et al. Oxidative stress induces increase in intracellular amyloid β-protein production and selective activation of βI and βII PKCs in NT2 cells. Biochem Biophys Res Commun. 2000;268:642–646
  160. Pappolla MA, Omar R, Kim K, Robakis N. Immunohistochemical evidence of oxidative [corrected] stress in Alzheimer's disease. Am J Pathol. 1992;149:1770
  161. Pappolla MA, Smith MA, Bryan-Thomas T, Bazan N, Petanceska S, Perry G, et al. Cholesterol, oxidative stress, and Alzheimer's disease: expanding the horizons of pathogenesis. Free Radic Biol Med. 2002;33:173–181
  162. Pearson RCA, Gatter KC, Powell TPS. Retrograde cell degeneration in the basal nucleus in monkey and man. Brain Res. 1983;261:321–326
  163. Perry G, Roder H, Nunomura A, Takeda A, Friedlich AL, Zhu X, et al. Activation of neuronal extracellular receptor kinases (ERK) in Alzheimer disease links oxidative stress to abnormal phosphorylation. Neuroreport. 1999;10:2411–2415
  164. Perry G, Taddeo MA, Nunomura A, Zhu X, Zenteno-Savin T, Drew KL, et al. Comparative biology and pathology of oxidative stress in Alzheimer and other neurodegenerative diseases: beyond damage and response. Comp Biochem Physiol Part C. 2002;133:507–513
  165. Perry G, Nunomura A, Hirai K, Zhu X, Pérez M, Avila J, et al. Is oxidative damage the fundamental pathogenic mechanic of Alzheimer's and other neurodegenerative diseases?. Free Radic Biol Med. 2002;33:1475–1479
  166. Perry G, Taddeo MA, Petersen RB, Castellani RJ, Harris PLR, Siedlak SL, et al. Adventiously-bound redox active iron and copper are at the center of oxidative damage in Alzheimer disease. Biometals. 2003;16:77–81
  167. Picklo MJ, Olson SJ, Hayes JD, Markesbery WR, Montine TJ. Elevation of AKR7A2 (succinic smialdehyde reductase) in neurodegenerative disease. Brain Res. 2001;916:229–238
  168. Picklo MJ, Olson SJ, Markesbery WR, Montine TJ. Expression and activities of aldo–keto oxidoreductases in Alzheimer disease. J Neuropathol Exp Neurol. 2001;60:686–695
  169. Picklo MJ, Montine TJ, Amarnath V, Neely MD. Carbonyl toxicology and Alzheimer's disease. Toxicol Appl Pharmacol. 2002;184:187–197
  170. Pierrefiche G, Topall G, Henriet I, Laborit H. Protective effects of gamma-hydroxybutyrate on alloxan induced diabetes in mice. Res Commun Chem Pathol Pharmacol. 1991;71:309–319
  171. Plant LD, Biyle JP, Smith IF, Peers C, Pearson HA. The production of amyloid β peptide is a critical requirement for the viability of central neurons. J Neurosci. 2003;23:5531–5535
  172. Pomara N, Singh R, Deptula D, Chou JCY, Schwartz MB, LeWitt PA. Glutamate and other CSF amino acids in Alzheimer's disease. Am J Psychiatry. 1992;149:251–254
  173. Popov VI, Bocharova LS. Hibernation-induced structural changes in synaptic contacts between mossy fibres and hippocampal pyramidal neurons. Neuroscience. 1992;48:53–62
  174. Popov VI, Bocharova LS, Bragin AG. Repeated changes of dendritic morphology in the hippocampus of ground squirrels in the course of hibernation. Neuroscience. 1992;48:45–51
  175. Popova NK, Ostrovskaya RV. Effect of gammaaminobutyric and gammahydroxybutyric acids on the awakening of sousliks from hibernation. Biulleten Eksperimentalhoi Biologii i Meditsiny. 1984;97:720–722
  176. Praticò D, Lee VMY, Trojanowski JQ, Rokach J, Fitzgerald GA. Increased F2-isoprostanes in Alzheimer's disease: evidence for enhanced lipid peroxidation in vivo. FASEB J. 1998;12:1777–1783
  177. Premkumar DRD, Smith MA, Richey PL, Petersen RB, Castellani RJ, Kutty K, et al. Induction of heme oxygenase-1 mRNA and protein in neocortex and cerebral vessels in Alzheimer's disease. J Neurochem. 1995;65:1399–1402
  178. Raina AK, Hochman A, Zhu X, Rottkamp CA, Nunomura A, Siedlak SL, et al. Abortive apoptosis in Alzheimer's disease. Acta Neuropathol. 2001;101:305–310
  179. Ramassamy C, Averill D, Beffert U, Bastianetto S, Theroux L, Lussier-Cacan S, et al. Oxidative damage and protection by antioxidants in the frontal cortex of Alzheimer's disease is related to the apolipoprotein E genotype. Free Radic Biol Med. 1999;27:544–553
  180. Rapoport S, Hatanpae K, Brady DR, Chandrasekaran K. Brain energy metabolism, cognitive function and down regulated oxidative phosphorylation in Alzheimer disease. Neurodegeneration. 1996;5:473–476
  181. Reiman EM, Caselli RJ, Yun LS, Chen K, Bandy D, Minoshima S, et al. Preclinical evidence of Alzheimer's disease in persons homozygous for the β4 allele for apolipoprotein E. N Engl J Med. 1996;334(∈4):752–758
  182. Reiman EM, Chen K, Alexander GE, Caselli RJ, Bandy D, Osborne D, et al. Functional brain Abnormalities in young adults at genetic risk for late-onset Alzheimer's dementia. PNAS. 2004;101:284–289
  183. Reimund E. The free radical flux theory of sleep. Med Hypoth. 1994;43:231–233
  184. Robert GW, Gentleman SM, Lynch A, Murray L, Landon M, Greahma DI. β amyloid protein deposition in the brain after severe head injury: implications for the pathogenesis of Alzheimer's disease. J Neurol Neurosurg Psychiatry. 1994;57:419–425
  185. Roher AE, Kuo YM, Kokjohn KM, Emmerling MR, Gracon S. Amyloid and lipids in the pathology of Alzheimer's disease. Amyloid. 1999;6:136–145
  186. Rottkamp CA, Nunomura A, Hirai K, Sayre LM, Perry G, Smith MA. Will antioxidants fulfill their expectations for the treatment of Alzheimer's disease?. Mech Ageing Dev. 2000;116:169–179
  187. Rottkamp CA, Raina AK, Zhu X, Gaier E, Bush AI, Atwood CS, et al. Redox-active iron mediates amyloid-β toxicity. Free Radic Biol Med. 2001;30:447–450
  188. Rottkamp CA, Atwood CS, Joseph JA, Nunomura A, Perry G, Smith MA. The state versus amyloid-β: the trial of the most wanted criminal in Alzheimer disease. Peptides. 2002;23:1333–1341
  189. Russell RL, Siedlak SL, Raina AK, Bautista JM, Smith MA, Perry G. Increased neuronal glucose-6-phosphate dehydrogenase and sulfhydryl levels indicate reductive compensation to oxidative stress in Alzheimer disease. Arch Biochem Biophys. 1999;370:236–239
  190. Salehi A, Delcroix J-D, Swaab DF. Alzheimer's disease and NGF signaling. J Neural Transm. 2004;111:323–345
  191. Sastre A, Sherriff F, McShane R. Memantine for dementia. Cochrane Database Syst Rev. 2005;3:1–103
  192. Saunders AM, Strittmatter WJ, Schemel D, St. George-Hystop PH, Pericak-Vance MA, Joo SH, et al. Association of apolipoprotein E allele ∈4 with late onset familial and sporadic Alzheimer disease. Neurology. 1993;43:1467–1472
  193. Scheff SW, Price DA. Synaptic pathology in Alzheimer's disease: a review of ultrastructural studies. Neurobiol Aging. 2003;24:1029–1046
  194. Schipper HM, et al. Expression of hemeoxygenase-1 in the senescent and Alzheimer diseased brain. Ann Neurol. 1995;37:758–768
  195. Schuler V, Lüscher C, Blanchet C, Klix N, Sansig G, Kiebs K, et al. Epilepsy, hyperalgesia, impaired memory, and loss of pre-and postsynaptic GABAB responses in mice lacking GABAB(1). Neuron. 2001;31:47–58
  196. Selkoe DJ. Alzheimer's disease: genes, proteins and therapy. Physiol Rev. 2001;81:741–766
  197. Selkoe DJ. Deciphering the genesis and fate of amyloid β-protein yields novel therapies for Alzheimer disease. J Clin Invest. 2002;110:1375–1381
  198. Sherman IA, Saibil FG, Janossy TI. β-hydroxybutyrate mediated protection of liver function after long-term hypothermic storage. Transplantation. 1994;57:8–11
  199. Sholokov VM, Baraniyazov Kh , Kizhaeva EV, Lyubimov BI, Samoilov NN, Yudin GV, et al. Effect of lithium oxybutyrate on the viability of preserved donor kidney. Farmakol Toksikol. 1986;49:69–70
  200. Shringarpure R, Grune T, Sitte N, Davies KJA. 4-Hydroxynonenal-modified amyloid-β peptide inhibits the proteasome: possible importance in Alzheimer's disease. Cell Mol Life Sci. 2000;57:1802–1809
  201. Simpson IA, Chundu KR, Davies-Hill T, Honer WG, Davies P. Decreased concentrations of GLUT1 and GLUT3 glucose Ttansporters in the brains of patients with Alzheimer's disease. Ann Neurol. 1994;35:546–551
  202. Sindou P, Lesort M, Couratier P, Yardin C, Esclaire F, Hugon J. Glutamate increases tau phosphorylation in primary neuronal cultures from fetal rat cerebral cortex. Brain Res. 1994;646:124–128
  203. Slivka A, Mytilineou C, Cohen G. Histochemical evaluation of glutathione in brain. Brain Res. 1987;409:275–284
  204. Slooter A, Crutz M, Kalmijn S, Hofman A, Breteler MMB, Van Broeckhoven C, et al. Risk estimates of dementia by apolipoprotein E genotypes from a population-based incidence study: the Rotterdam Study. Arch Neurol. 1998;55:964–968
  205. Smith MA, Taneda S, Richey Harris PL, et al. Advanced Maillard reaction and products are associated with Alzheimer disease pathology. PNAS. 1994;91:5710–5714
  206. Smith MA, Richey Harris PL, Sayre LM, Beckman JS, Perry G. Widespread peroxynitrite-mediated damage in Alzheimer's disease. J Neurosci. 1997;17(8):2653–2657
  207. Smith MA, Casadesus G, Joseph JA, Perry G. Amyloid β and τ serve antioxidant functions in the aging and Alzheimer brain. Free Radic Biol Med. 2002;33:1194–2002
  208. Sofroniew MV, Pearson RCA, Eckenstein F, Cuello AC, Powell TPS. Retrograde changes in cholinergic neurons in the basal forebrain of the rat following cortical damage. Brain Res. 1983;289:370–374
  209. Sofroniew MV, Howe CL, Mobley WC. Nerve growth factor signaling, neuroprotection, and neural repair. Annu Rev Neurosci. 2001;24:1217–1281
  210. Spatz M, Abe K, Smialek M, Abe T. Evaluation of gamma-hydroxybutyrate treatment in experimental cerebral ischemia. In:  Betz E,  Grote J editor. Pathophysiology and pharmacotherapy of cerebrovascular disorders. Baden/Baden: G.W. Witztrock; 1980;p. 286–289
  211. Stokin G, Lillo C, Falzone TL, Brusch RG, Rockenstein E, Mount SL, et al. Axonopathy and transport deficits early in the pathogenesis of Alzheimer's disease. Science. 2005;307:1282–1288
  212. Storey KB, Storey JM. Biochemical adaptation to extreme environments. In:  Walz W editors. Integrative physiology: in the proteomics and post-genomics age. Totowa, NJ: Humana Press Inc.; 2005;p. 169–200
  213. Taberner PV, Rick JT, Kerkut GA. The Action of gamma-hydroxybutyric acid on cerebral glucose metabolism. J Neurochem. 1972;19:245–254
  214. Taberner PV. Effects of gammahydroxybutyric acid and other hypnotics on glucose uptake in vivo and in vitro. J Neurochem. 1973;20:669–680
  215. Takeda A, Smith MA, Avila J, Nomura A, Siedlak SL, Zhu X, et al. In Alzheimer's disease, heme oxygenase is coincident with Alz 50, an epitope of tau induced by 4 hydroxynonenal modification. J Neurochem. 2000;75:1234–1241
  216. Tamagna E, Parola M, Bardini P, Piccini A, Borghi R, Guglielmotto M, et al. β-Site APP cleaving enzyme up-regulation induced by 4-hydroxynonenal is mediated by stress activated protein kinase pathways. J Neurochem. 2005;92:628–636
  217. Tanaka T, Minamino H, Unezaki S, Tsukatani H, Tokumura A. Formation of platelet-activating factor-like phospholipids by Fe2+/ascorbate/EDTA-induced lipid peroxidation. Biochim Biophys Acta. 1993;1166:264–274
  218. Teller JK, Russo C, DeBusk LM, Angelini G, Zaccheo D, Dagna-Bricarelli F, et al. Presence of soluble amyloid β-peptide precedes amyloid plaque formation in Down's syndrome. Nat Med. 1996;2:93–95
  219. Terry RD. The cytoskeleton in Alzheimer disease. J Neural Transm. 1998;53:141–145
  220. Thomas T, Thomas G, McLendon C, Sutton T, Mullan M. β-Amyloid-mediated vasoactivity and vascular endothelial damage. Nature. 1996;380:168–171
  221. Timmerman W, Westerink BHC. Brain microdialysis of GABA and glutamate: what does it signify?. Synapse. 1997;27:242–261
  222. Tiraboschi P, Hansen LA, Alford M, Masliah E, Thal LJ, Corey-Bloom J. The decline in synapses and cholinergic activity is asynchronous in Alzheimer's disease. Neurology. 2000;55:1278–1283
  223. Tobler I. Phylogeny of sleep regulation. In:  Kryger MH,  Roth T,  Dement WC editor. Principles and practice of sleep medicine. 3rd ed.. Toronto: W.B. Saunders Co.; 2003;p. 72–81
  224. Tokumura A, Tanaka T, Yotsumoto T, Tsukatani H. Identification of sn-2-ω-hydroxycarboxylate-containing phopholipids in a lipid extract from bovine brain. Biochem Biophys Res Commun. 1991;177:466–473
  225. Van Cauter E, Plat L, Scharf MB, Leproult R, Cespedes S, L’Hermite-Balériaux M, et al. Simultaneous stimulation of slow-wave sleep and growth hormone secretion by gamma-hydroxybutyrate in normal young men. J Clin Invest. 1997;100:745–753
  226. Varadarajan S, Yatin S, Kanski J, Jahanshahi F, Butterfield DA. Methionine residue 35 is important in amyloid β-peptide-associated free radical oxidative stress. Brain Res Bull. 1999;50:133–141
  227. Vergoni AV, Ottani A, Botticelli AR, Zaffe D, Guano L, Loche A, et al. Neuroprotective effect of γ-hydroxybutyrate in transient global cerebral ischemia in the rat. Eur J Pharmacol. 2000;397:75–84
  228. Vitiello MV, Prinz PN, Williams DE, Frommlet MS, Ries RK. Sleep disturbances in patients with mild-stage Alzheimer's disease. J Gerontol. 1990;45:M131–M138
  229. Walkenstein SS, Wiser R, Gudmundsen C, Kimmel H. Metabolism of gammahydroxybutyric acid. Biochem Biophys Acta. 1964;86:640–642
  230. Wang D-S, Iwata N, Hama E, Saido TC, Dickson DW. Oxidized neprilysin in aging and Alzheimer's disease brains. Biochem Biophys Res Commun. 2003;310:236–241
  231. Wei C-Z, Xia S-S. γ-Hydroxybutyrate protects the liver from warm ischemia-reperfusion injury in rat. Hepatob Pancreatic Dis Int. 2004;3:245–249
  232. Wolfson LI, Sakurada O, Sokoloff L. Effects of γ-butyrolactone on local cerebral glucose utilization in the rat. J Neurochem. 1977;29:777–783
  233. Wong TP, Debeir T, Duff K, Cuello AC. Reorganization of cholinergic terminals in the cerebral cortex and hippocampus in transgenic mice carrying mutated presenilin-1 and amyloid precursor protein transgenes. J Neurosci. 1999;19:2706–2716
  234. Xie X, Smart TG. Gammahydroxybutyrate depresses monosynaptic excitatory and inhibitory postsynaptic potentials in rat hippocampal slices. Eur J Pharmacol. 1992;223:193–196
  235. Xie X, Smart TG. Gammahydroxybutyrate hyperpolarizes hippocampal neurones by activating GABAB receptors. Eur J Pharmacol. 1992;212:291–294
  236. Xu H, Sweeney D, Wang R, Thinakaran G, Lo A, Sisodia SS, et al. Generation of Alzheimer beta-amyloid protein in the trans-Golgi network in the apparent absence of vesicle formation. PNAS. 1997;94:3748–3752
  237. Yamasaki N, Oka T, Yamamoto S, Nagayasu T, Akamine S, Takahashi T, et al. Twenty-four-hour preservation in γ-hydroxybutyrate improves lung function in a cainine single-lung allotransplantation. Transplantation. 1999;67:529–533
  238. Yan SD, Chen X, Schmidt AM, Brett J, Godman G, Zou Y-S, et al. Glycated tau protein in Alzheimer disease: a mechanism for induction of oxidant stress. PNAS. 1994;91:7787–7791
  239. Yan SD, Yan SF, Chen X, Fu J, Chen M, Kuppusamy P, et al. Non-enzymatically glycated tau in Alzheimer's disease induces neuronal oxidant stress resulting in cytokine gene expression and release of amyloid β-peptide. Nat Med. 1995;1:693–699
  240. Yosunkaya A, Ak A, Bariskaner H, Üstün ME, Tuncer S, Gürbilek M. Effect of gamma-hydroxybutyric acid on lipid peroxidation and tissue lactate level in experimental head trauma. J Trauma Injury Infect Crit Care. 2004;56:585–590
  241. Zaczek R, Nelson M, Coyle JT. Kainic acid neurotoxicity and seizures. Neuropharmacology. 1981;20:183–189
  242. Zecca L, Youdim MBH, Riederer P, Connor JR, Crichton RR. Iron, brain ageing and neurodegenerative disorders. Nat Rev. 2004;5:863–873
  243. Zhu X, Castellani RJ, Takeda A, Nomura A, Atwood CS, Perry G, et al. Differential activation of neuronal ERK, JNK/SAPK and p38 in Alzheimer disease: the “two hit” hypothesis. Mech Aging Dev. 2001;123:39–46
  244. Zhu X, Raina AK, Lee H, Casadesus G, Smith MA, Perry G. Oxidative stress signaling in Alzheimer's disease. Brain Res. 2004;1000:38–39

PII: S0197-4580(06)00220-X

doi: 10.1016/j.neurobiolaging.2006.06.008

Neurobiology of Aging
Volume 28, Issue 9 , Pages 1340-1360 , September 2007