title: Death by a thousand cuts in Alzheimer's disease: hypoxia--the prodrome.
abstract: A wide range of clinical consequences may be associated with obstructive sleep apnea (OSA) including systemic hypertension, cardiovascular disease, pulmonary hypertension, congestive heart failure, cerebrovascular disease, glucose intolerance, impotence, gastroesophageal reflux, and obesity, to name a few. Despite this, 82 % of men and 93 % of women with OSA remain undiagnosed. OSA affects many body systems, and induces major alterations in metabolic, autonomic, and cerebral functions. Typically, OSA is characterized by recurrent chronic intermittent hypoxia (CIH), hypercapnia, hypoventilation, sleep fragmentation, peripheral and central inflammation, cerebral hypoperfusion, and cerebral glucose hypometabolism. Upregulation of oxidative stress in OSA plays an important pathogenic role in the milieu of hypoxia-induced cerebral and cardiovascular dysfunctions. Strong evidence underscores that cerebral amyloidogenesis and tau phosphorylation--two cardinal features of Alzheimer's disease (AD), are triggered by hypoxia. Mice subjected to hypoxic conditions unambiguously demonstrated upregulation in cerebral amyloid plaque formation and tau phosphorylation, as well as memory deficit. Hypoxia triggers neuronal degeneration and axonal dysfunction in both cortex and brainstem. Consequently, neurocognitive impairment in apneic/hypoxic patients is attributable to a complex interplay between CIH and stimulation of several pathological trajectories. The framework presented here helps delineate the emergence and progression of cognitive decline, and may yield insight into AD neuropathogenesis. The global impact of CIH should provide a strong rationale for treating OSA and snoring clinically, in order to ameliorate neurocognitive impairment in aged/AD patients.
authors: Sleep Disorders Group, EEE Department, Melbourne School of Engineering, The University of Melbourne, 3rd Floor, Room # 344, Parkville, VIC 3010, Australia. mak@drmakdaulatzai.us
authors: Mak Adam
authors: MA
authors: Daulatzai
mesh_terms: D000544:Alzheimer Disease / Q000453:epidemiology / Q000378:metabolism / Q000473:pathology*; D000818:Animals; D016923:Cell Death / Q000502:physiology; D006801:Humans; D002534:Hypoxia, Brain / Q000453:epidemiology / Q000378:metabolism / Q000473:pathology*; D062706:Prodromal Symptoms; D020181:Sleep Apnea, Obstructive / Q000453:epidemiology / Q000378:metabolism / Q000473:pathology*
references: J Neurosci Res. 2008 Jun;86(8):1768-80
references: 18293416
references: Med Sci Monit. 2005 Mar;11(3):RA70-5
references: 15735578
references: Exp Neurol. 2012 Dec;238(2):176-82
references: 22960186
references: Sleep. 2010 Feb;33(2):205-10
references: 20175404
references: J Appl Physiol (1985). 1993 Jun;74(6):2828-37
references: 8365987
references: J Physiol. 2009 Jul 1;587(Pt 13):3287-99
references: 19417094
references: Chest. 1992 Nov;102(5):1402-6
references: 1424859
references: J Alzheimers Dis. 2007 Dec;12(4):335-41
references: 18198420
references: Free Radic Biol Med. 2001 Jun 1;30(11):1191-212
references: 11368918
references: Am J Respir Crit Care Med. 2010 Dec 15;182(12):1540-5
references: 20656942
references: Angiology. 1999 Mar;50(3):201-8
references: 10088799
references: Rev Med Interne. 2003 Mar;24(3):165-71
references: 12657438
references: Acta Neuropathol. 1995;90(5):461-6
references: 8560978
references: Am J Respir Crit Care Med. 1999 Jan;159(1):213-9
references: 9872841
references: Hypertension. 1988 Aug;12(2):89-95
references: 3044994
references: Clin Endocrinol (Oxf). 2006 Jan;64(1):12-9
references: 16402923
references: Stroke. 1998 Jan;29(1):87-93
references: 9445334
references: Neurosci Lett. 2008 Jun 27;438(3):330-4
references: 18486338
references: Mol Cell Biol. 1996 Sep;16(9):4604-13
references: 8756616
references: Am J Physiol Regul Integr Comp Physiol. 2009 Nov;297(5):R1283-92
references: 19726713
references: Sleep. 1993 Jan;16(1):40-81
references: 8456235
references: Sleep. 2004 Feb 1;27(1):123-8
references: 14998248
references: Adv Exp Med Biol. 2012;748:145-69
references: 22729857
references: Neurology. 1996 Jan;46(1):154-9
references: 8559366
references: Am J Respir Crit Care Med. 2005 Oct 15;172(8):1056-7; author reply 1057-8
references: 16216840
references: Sleep Med. 2009 Sep;10(8):875-81
references: 19200779
references: Neurochem Res. 2012 Dec;37(12):2627-58
references: 22886562
references: Sleep Breath. 2009 Mar;13(1):89-92
references: 18682999
references: Best Pract Res Clin Endocrinol Metab. 2010 Oct;24(5):843-51
references: 21112030
references: Thorax. 1995 Nov;50(11):1136-40
references: 8553267
references: Neurobiol Aging. 2000 Mar-Apr;21(2):207-14
references: 10867205
references: Circulation. 2010 Mar 2;121(8):1014-21
references: 20159829
references: J Biol Chem. 1988 Feb 25;263(6):2712-8
references: 2830260
references: Neurosci Lett. 2010 May 3;474(3):173-177
references: 20304032
references: Alzheimers Dement. 2013 Sep;9(5):512-8
references: 23142434
references: Exp Neurol. 2009 Apr;216(2):290-4
references: 19124019
references: Stroke. 2007 Jun;38(6):1766-73
references: 17510458
references: Cell Mol Neurobiol. 2005 Jun;25(3-4):485-512
references: 16075377
references: Age (Dordr). 2013 Jun;35(3):777-92
references: 22544617
references: Adv Exp Med Biol. 2013;765:131-138
references: 22879025
references: Curr Hypertens Rep. 2009 Jun;11(3):212-6
references: 19442331
references: Mol Chem Neuropathol. 1991 Oct;15(2):117-42
references: 1663746
references: J Mol Neurosci. 2011 Feb;43(2):155-61
references: 20711757
references: J Neurol Sci. 2013 Jan 15;324(1-2):124-30
references: 23146611
references: Sleep Med Rev. 2003 Feb;7(1):35-51
references: 12586529
references: FASEB J. 2006 Jul;20(9):1361-8
references: 16816111
references: Br Med J (Clin Res Ed). 1987 Jan 3;294(6563):16-9
references: 3101779
references: J Appl Physiol (1985). 2005 Dec;99(6):2440-50
references: 16288102
references: J Physiol. 1997 Jul 1;502 ( Pt 1):161-74
references: 9234204
references: Haemostasis. 1993 Mar;23 Suppl 1:118-26
references: 8495863
references: J Neurochem. 2009 Feb;108(4):1045-56
references: 19196431
references: J Laryngol Otol. 2009 Feb;123(2):203-7
references: 18549514
references: Sleep Breath. 2012 Jun;16(2):349-54
references: 21360253
references: Exp Brain Res. 2003 Feb;148(3):320-7
references: 12541143
references: Neurology. 2008 Feb 5;70(6):440-8
references: 17942819
references: Am J Physiol Regul Integr Comp Physiol. 2006 Apr;290(4):R1105-14
references: 16322350
references: J Biol Chem. 1998 May 29;273(22):13379-82
references: 9593665
references: Brain. 2012 Dec;135(Pt 12):3749-56
references: 23204143
references: J Cereb Blood Flow Metab. 2007 Dec;27(12):1908-18
references: 17429347
references: J Alzheimers Dis. 2012;28(3):567-78
references: 22045482
references: J Appl Physiol (1985). 2006 Jun;100(6):1974-82
references: 16484362
references: Brain Res. 2006 May 1;1086(1):152-9
references: 16595126
references: Neurobiol Aging. 2004 Jul;25(6):783-93
references: 15165703
references: Am J Pathol. 2010 Jul;177(1):300-10
references: 20472896
references: Nat Immunol. 2009 Feb;10(2):195-202
references: 19122655
references: Neurology. 2009 May 19;72(20):1720-6
references: 19228583
references: Hypertension. 2010 Sep;56(3):369-77
references: 20625082
references: J Cereb Blood Flow Metab. 2011 May;31(5):1223-8
references: 21304554
references: Neurobiol Aging. 2011 May;32(5):763-77
references: 19464758
references: Arch Neurol. 2009 Feb;66(2):216-25
references: 19204158
references: J Hypertens. 1999 Jan;17(1):61-6
references: 10100095
references: Neurology. 2002 Aug 13;59(3):321-6
references: 12177363
references: Stroke. 1993 Dec;24(12):2121-7
references: 8248999
references: Nutr Metab Cardiovasc Dis. 2009 Mar;19(3):184-9
references: 18805681
references: Brain Res. 2003 Sep 26;985(2):127-34
references: 12967716
references: Sleep Breath. 2011 Dec;15(4):845-54
references: 21136300
references: Cell Res. 2004 Dec;14(6):467-72
references: 15625013
references: Am J Respir Crit Care Med. 2002 Nov 15;166(10):1382-7
references: 12421746
references: J Anat. 2008 Feb;212(2):106-13
references: 18069990
references: Neurol Res. 2003 Sep;25(6):635-41
references: 14503018
references: J Alzheimers Dis. 2011;26(2):315-29
references: 21628793
references: Am J Respir Crit Care Med. 1994 Dec;150(6 Pt 1):1587-91
references: 7952619
references: Thorax. 2000 Dec;55(12):1046-51
references: 11083891
references: J Neurotrauma. 2002 Jan;19(1):85-98
references: 11852981
references: J Neurochem. 1993 Jul;61(1):57-67
references: 8515288
references: Hypertension. 2004 May;43(5):1074-9
references: 15007032
references: J Cereb Blood Flow Metab. 2002 May;22(5):569-75
references: 11973429
references: Lancet. 2005 Mar 19-25;365(9464):1046-53
references: 15781100
references: Amino Acids. 2008 Aug;35(2):339-43
references: 18163181
references: Brain Res. 1996 Feb 5;708(1-2):82-92
references: 8720862
references: J Appl Physiol (1985). 1992 May;72(5):1978-84
references: 1601808
references: Mol Neurobiol. 2002 Oct-Dec;26(2-3):283-98
references: 12428761
references: Arch Biochem Biophys. 1985 Mar;237(2):408-14
references: 2983613
references: Stroke. 1994 Mar;25(3):601-7
references: 8128513
references: N Engl J Med. 1993 Apr 29;328(17):1230-5
references: 8464434
references: Science. 2009 Nov 13;326(5955):1005-7
references: 19779148
references: J Neurosci. 2002 Jan 1;22(1):209-17
references: 11756504
references: FEBS J. 2006 Feb;273(3):433-50
references: 16420469
references: Neurology. 1998 Jul;51(1):159-62
references: 9674796
references: Am J Physiol Lung Cell Mol Physiol. 2002 Nov;283(5):L922-31
references: 12376345
references: Sleep Breath. 2005 Dec;9(4):176-80
references: 16283228
references: Biochem Biophys Res Commun. 2007 Dec 7;364(1):100-4
references: 17927959
references: J Neurol Sci. 1998 Jul 15;159(1):45-50
references: 9700702
references: Eur Neurol. 2009;62(4):237-42
references: 19672077
references: Brain. 1984 Sep;107 ( Pt 3):935-50
references: 6478183
references: J Clin Sleep Med. 2011 Dec 15;7(6):616-21
references: 22171200
references: J Neurosci. 2003 Mar 1;23(5):1710-8
references: 12629175
references: ScientificWorldJournal. 2009 Aug 11;9:781-91
references: 19705038
references: Hypertension. 2007 Oct;50(4):630-5
references: 17785628
references: Brain Res Mol Brain Res. 1999 Jul 23;71(1):11-22
references: 10407182
references: J Pharmacol Exp Ther. 2002 Feb;300(2):408-16
references: 11805198
references: Med Clin North Am. 1985 Nov;69(6):1221-42
references: 3906301
references: Transl Res. 2010 Jan;155(1):35-43
references: 20004360
references: Neurosci Res. 2011 Feb;69(2):161-73
references: 20969897
references: Pneumologie. 1997 Sep;51(9):926-30
references: 9411446
references: PLoS One. 2011;6(5):e19847
references: 21625437
references: Sleep. 2004 Mar 15;27(2):194-201
references: 15124711
references: J Neurophysiol. 1997 Aug;78(2):891-902
references: 9307122
references: Hypertension. 2012 Nov;60(5):1324-31
references: 23045461
references: Adv Exp Med Biol. 2009;648:319-28
references: 19536495
references: Proc Natl Acad Sci U S A. 1995 Mar 14;92(6):1989-93
references: 7892213
references: Neuroimage. 2011 Jan 15;54(2):787-93
references: 20888921
references: PLoS Med. 2009 Aug;6(8):e1000132
references: 19688045
references: J Neurol Neurosurg Psychiatry. 2001 May;70(5):685-7
references: 11309469
references: Mol Cell Biol. 2002 Jan;22(1):94-104
references: 11739725
references: Am J Respir Crit Care Med. 2011 May 15;183(10):1419-26
references: 21037021
references: Curr Alzheimer Res. 2007 Apr;4(2):147-52
references: 17430239
references: J Neural Transm (Vienna). 2006 Nov;113(11):1723-32
references: 16752046
references: Neurobiol Aging. 2013 Mar;34(3):663-78
references: 22795785
references: Alzheimers Dement. 2007 Jul;3(3):186-91
references: 19595937
references: Sleep. 2007 Dec;30(12):1747-55
references: 18246984
references: Nat Rev Cardiol. 2010 Dec;7(12):677-85
references: 21079639
references: Sleep Med. 2009 Sep;10(8):887-91
references: 19231280
references: Stroke. 2006 Sep;37(9):2220-41
references: 16917086
references: Am J Physiol Regul Integr Comp Physiol. 2003 Apr;284(4):R893-912
references: 12626356
references: Am J Respir Crit Care Med. 2000 Aug;162(2 Pt 1):566-70
references: 10934088
references: Circulation. 2000 Nov 21;102(21):2607-10
references: 11085964
references: Clin Auton Res. 2012 Feb;22(1):1-8
references: 21796355
references: J Neurosci. 2001 Apr 1;21(7):2442-50
references: 11264318
references: J Exp Med. 1995 Mar 1;181(3):1179-86
references: 7532680
references: J Neuropathol Exp Neurol. 2011 Mar;70(3):201-17
references: 21293297
references: Neurochem Int. 2002 May;40(6):511-26
references: 11850108
references: Hypertens Res. 2012 Aug;35(8):855-61
references: 22573204
references: Cell Mol Life Sci. 2009 Nov;66(22):3555-63
references: 19763399
references: Sleep Breath. 2012 Jun;16(2):571-8
references: 21681412
references: Eur Respir J. 2011 Nov;38(5):1089-97
references: 21622590
references: FASEB J. 2009 Aug;23(8):2459-66
references: 19346295
references: PLoS One. 2011 Jan 27;6(1):e16567
references: 21305033
references: Ann N Y Acad Sci. 1997 Sep 26;826:128-46
references: 9329686
references: Am J Physiol Lung Cell Mol Physiol. 2009 Oct;297(4):L596-607
references: 19592458
references: Respir Physiol Neurobiol. 2002 Aug 22;132(1):17-41
references: 12126693
references: Sleep Med. 2007 Sep;8(6):623-36
references: 17383938
references: J Sleep Res. 2004 Mar;13(1):79-86
references: 14996039
references: Respir Med. 2008 Oct;102(10):1412-6
references: 18606532
references: J Neurosci. 2006 Feb 1;26(5):1343-54
references: 16452658
references: Exp Gerontol. 1997 Jul-Oct;32(4-5):441-50
references: 9315448
references: Am J Respir Crit Care Med. 2001 Apr;163(5):1181-90
references: 11316657
references: J Neurosci Res. 1995 Jul 1;41(4):561-6
references: 7473888
references: N Engl J Med. 2009 Jan 8;360(2):140-9
references: 19129527
references: Proc Natl Acad Sci U S A. 2009 Jan 27;106(4):1255-60
references: 19171901
references: EMBO Mol Med. 2012 Jul;4(7):660-73
references: 22488900
references: J Biol Chem. 2003 Sep 26;278(39):37681-9
references: 12821672
references: Exp Physiol. 2007 Jan;92(1):79-85
references: 17085676
references: Expert Rev Neurother. 2010 Nov;10(11):1667-73
references: 20977325
references: Nat Rev Neurosci. 2011 Nov 03;12(12):723-38
references: 22048062
references: Neurobiol Aging. 2012 Apr;33(4):827.e11-9
references: 21821316
references: J Appl Physiol (1985). 2008 Dec;105(6):1852-7
references: 18927265
references: J Neurochem. 2001 May;77(3):953-6
references: 11331424
references: Adv Cardiol. 2011;46:139-170
references: 22005191
references: Endeavour. 1995;19(3):96-100
references: 7493592
references: Am J Respir Crit Care Med. 2005 Oct 1;172(7):921-9
references: 15994465
references: Arterioscler Thromb Vasc Biol. 2007 Feb;27(2):303-9
references: 17138940
references: Neurotox Res. 2012 Oct;22(3):208-19
references: 22002808
references: Nat Med. 2003 Jan;9(1):3-4
references: 12514700
references: Brain Res. 2009 Oct 19;1294:202-10
references: 19646974
references: Physiol Rev. 2010 Jan;90(1):47-112
references: 20086074
references: Trends Cardiovasc Med. 2008 Oct;18(7):253-60
references: 19232954
references: Eur Respir J. 2002 Aug;20(2):444-50
references: 12212980
references: PLoS One. 2011;6(11):e27762
references: 22114686
references: J Sleep Res. 2012 Apr;21(2):147-54
references: 21895822
references: Biochem Biophys Res Commun. 2006 Aug 4;346(3):727-38
references: 16777064
references: Am Rev Respir Dis. 1993 Aug;148(2):418-24
references: 8342906
references: J Clin Invest. 2007 Nov;117(11):3393-402
references: 17965777
references: Cell Metab. 2008 Jun;7(6):476-84
references: 18522829
references: Electroencephalogr Clin Neurophysiol. 1986 Jan;63(1):10-7
references: 2416530
references: Ann N Y Acad Sci. 2002 Nov;977:65-76
references: 12480734
references: Am J Respir Crit Care Med. 2002 May 1;165(9):1217-39
references: 11991871
references: Mol Med. 2004 Jan-Jun;10(1-6):28-35
references: 15502880
references: J Cereb Blood Flow Metab. 1996 Nov;16(6):1219-23
references: 8898694
references: Proc Natl Acad Sci U S A. 2011 Aug 9;108(32):13147-52
references: 21788507
references: Blood. 2008 Feb 15;111(4):2024-35
references: 18056839
references: Am J Respir Crit Care Med. 2003 Jun 1;167(11):1548-53
references: 12615622
references: Sleep Breath. 2012 Jun;16(2):309-12
references: 21553349
references: Adv Exp Med Biol. 2006;588:75-88
references: 17089881
references: Arterioscler Thromb Vasc Biol. 2007 Jun;27(6):1269-75
references: 17413034
references: Clin Hemorheol Microcirc. 2005;33(4):369-77
references: 16317246
references: Neuron. 1991 Dec;7(6):1031-41
references: 1662517
references: Eur Heart J. 2004 May;25(9):735-41
references: 15120883
references: J Neurosci. 1994 Sep;14(9):5373-80
references: 8083742
references: Neurosci Lett. 2011 Feb 4;489(2):84-8
references: 21134418
references: Life Sci. 2002 Jan 4;70(7):821-31
references: 11833744
references: Heart Fail Rev. 2009 Sep;14(3):143-53
references: 18807180
references: Pediatr Res. 2008 Apr;63(4):364-9
references: 18356740
references: Curr Opin Nephrol Hypertens. 2011 Jan;20(1):50-5
references: 21326007
references: Sleep Breath. 2012 Mar;16(1):217-21
references: 21331508
references: Sleep Med Rev. 2009 Jun;13(3):187-94
references: 18848476
references: Adv Exp Med Biol. 2007;618:51-67
references: 18269188
references: Eur Arch Otorhinolaryngol. 2010 Jul;267(7):1147-56
references: 19949955
references: Am J Geriatr Psychiatry. 2005 May;13(5):359-68
references: 15879584
references: Am J Respir Crit Care Med. 2002 Aug 15;166(4):479-84
references: 12186824
references: Stroke. 1990 Oct;21(10):1464-9
references: 2219212
references: Arch Intern Med. 2006 Sep 18;166(16):1756-62
references: 16983055
references: J Biol Chem. 1998 May 8;273(19):11619-24
references: 9565580
references: J Exp Med. 2004 Dec 6;200(11):1395-405
references: 15583013
references: Proc Natl Acad Sci U S A. 2006 Dec 5;103(49):18727-32
references: 17121991
references: Front Neural Circuits. 2012 Aug 09;6:51
references: 22907993
references: Hypertension. 2008 Nov;52(5):841-6
references: 18838624
references: Sleep Med Rev. 2003 Aug;7(4):297-310
references: 14505597
references: Am J Respir Crit Care Med. 2002 Mar 1;165(5):670-6
references: 11874812
references: J Appl Physiol (1985). 2007 Feb;102(2):557-63
references: 17082365
references: FEBS J. 2005 Jul;272(14):3593-601
references: 16008559
references: Biochem J. 1984 Apr 1;219(1):1-14
references: 6326753
references: J Neural Transm Suppl. 2002;(63):91-109
references: 12597611
references: Am J Respir Crit Care Med. 2002 Apr 1;165(7):934-9
references: 11934717
references: Sleep Med. 2010 Oct;11(9):837-42
references: 20719563
references: Neuroreport. 1996 Nov 4;7(15-17):2727-31
references: 8981456
references: Neurobiol Aging. 2009 Jul;30(7):1091-8
references: 18063223
references: Curr Alzheimer Res. 2013 Mar;10(3):298-308
references: 23036024
references: Exp Neurol. 1992 Aug;117(2):114-23
references: 1323483
references: Eur Respir J. 2011 Jul;38(1):89-97
references: 20847078
references: Neurobiol Dis. 2010 Oct;40(1):251-64
references: 20554036
references: J Cereb Blood Flow Metab. 1999 Nov;19(11):1238-46
references: 10566970
references: Brain Res. 2000 Jan 17;853(1):1-4
references: 10627301
references: J Neurosci. 2005 Feb 16;25(7):1769-77
references: 15716413
references: J Hypertens. 2007 May;25(5):1021-6
references: 17414666
references: Eur J Clin Invest. 1991 Feb;21(1):72-6
references: 1907558
references: Arch Gerontol Geriatr. 1982 Sep;1(2):101-16
references: 6821143
references: Neurobiol Aging. 2009 Aug;30(8):1276-87
references: 18160181
references: Curr Opin Genet Dev. 1998 Oct;8(5):588-94
references: 9794818
references: Neurobiol Aging. 2004 Mar;25(3):283-90
references: 15123332
references: Ann N Y Acad Sci. 1997 Sep 26;826:401-5
references: 9329712
references: Autoimmunity. 2006 May;39(3):177-90
references: 16769651
references: Prog Brain Res. 2011;190:53-68
references: 21531244
references: Trends Neurosci. 1988 Oct;11(10):465-9
references: 2469166
references: Neurochem Res. 2009 Jul;34(7):1226-35
references: 19123057
references: J Neurol Sci. 2002 Mar 15;195(1):11-23
references: 11867069
references: Neuroscience. 2007 Aug 10;148(1):325-33
references: 17630219
references: J Alzheimers Dis. 2010;20(2):355-67
references: 20164576
references: Hypertension. 1992 Jun;19(6 Pt 1):555-61
references: 1592450
references: Acta Otolaryngol. 1999;119(8):925-33
references: 10728936
references: J Appl Physiol (1985). 2001 May;90(5):1995-9
references: 11299294
references: Naunyn Schmiedebergs Arch Pharmacol. 2012 Oct;385(10):953-9
references: 22872171
references: Ann N Y Acad Sci. 1994 Dec 15;747:50-76
references: 7847692
references: Nat Rev Drug Discov. 2005 May;4(5):421-40
references: 15864271
references: J Sleep Res. 2009 Mar;18(1):36-48
references: 19250174
references: J Neurochem. 2007 Aug;102(3):900-12
references: 17561941
references: Neurol Res. 1992;14(2 Suppl):128-31
references: 1355868
references: Stroke. 1996 Aug;27(8):1283-9
references: 8711787
references: J Hypertens. 2001 May;19(5):913-9
references: 11393675
references: Neuroscience. 2004;126(2):313-23
references: 15207349
references: Lancet. 1985 Dec 14;2(8468):1325-6
references: 2866387
references: Stroke. 2011 Sep;42(9):2595-604
references: 21737797
references: J Neurochem. 2006 Aug;98(4):1167-75
references: 16762022
references: J Neurosci Res. 2009 Aug 15;87(11):2561-70
references: 19360903
references: Science. 2003 Dec 5;302(5651):1760-5
references: 14615545
references: Annu Int Conf IEEE Eng Med Biol Soc. 2011;2011:3209-12
references: 22255022
references: J Neurol Sci. 1991 Nov;106(1):105-11
references: 1685745
references: Rev Neurol (Paris). 1998 Apr;154(3):208-16
references: 9773044
references: Exp Neurol. 2010 Jun;223(2):299-303
references: 19679125
references: Neurobiol Aging. 2001 Nov-Dec;22(6):837-42
references: 11754990
references: Chest. 1996 Apr;109(4):916-21
references: 8635370
references: N Engl J Med. 2005 Nov 10;353(19):2034-41
references: 16282178
references: Sleep. 2007 Feb;30(2):225-7
references: 17326549
references: J Alzheimers Dis. 2010;21(4):1039-63
references: 21504131
references: Thromb Haemost. 2008 Oct;100(4):576-81
references: 18841278
references: Physiol Rev. 1997 Oct;77(4):1081-132
references: 9354812
references: Nutr Rev. 2010 Dec;68 Suppl 2:S74-87
references: 21091952
references: Respir Physiol Neurobiol. 2006 Mar 28;151(1):44-60
references: 15993658
references: Sleep. 2007 Sep;30(9):1145-52
references: 17910386
references: J Biol Chem. 2012 Oct 12;287(42):35222-35233
references: 22910909
references: J Alzheimers Dis. 2006 Sep;10(1):89-109
references: 16988486
references: Trends Pharmacol Sci. 1989 Jul;10(7):281-5
references: 2672472
references: Eur J Neurol. 2010 Nov;17(11):1326-38
references: 20443977
references: Am J Pathol. 2004 Feb;164(2):719-25
references: 14742275
references: J Am Coll Cardiol. 1999 Nov 15;34(6):1744-9
references: 10577565
references: Front Neurol. 2012 Jan 30;3:7
references: 22319509
references: Pflugers Arch. 2010 May;459(6):923-39
references: 20306272
references: Expert Rev Neurother. 2009 May;9(5):681-93
references: 19402778
references: Respir Physiol Neurobiol. 2003 Nov 14;138(2-3):275-90
references: 14609516
references: Diabetologia. 1990 May;33(5):311-8
references: 2376302
references: Curr Pharm Des. 2008;14(32):3430-45
references: 19075719
references: Circ Res. 2004 Nov 12;95(10):1019-26
references: 15499027
references: Ann Neurol. 1986 Feb;19(2):105-11
references: 2421636
references: J Neurol. 2012 Jul;259(7):1433-9
references: 22215237
references: Sleep Med. 2012 Jan;13(1):15-20
references: 22137116
references: Arch Neurol. 2002 Sep;59(9):1381-9
references: 12223024
references: Stroke. 2003 Aug;34(8):2038-42
references: 12829858
references: J Sleep Res. 2007 Jun;16(2):217-25
references: 17542952
references: Brain Res. 1992 Jun 5;582(1):107-18
references: 1354011
references: J Alzheimers Dis. 2010;21(3):813-22
references: 20634588
references: Biochim Biophys Acta. 2009 May;1792(5):432-43
references: 19135149
references: Brain Behav Immun. 2006 May;20(3):246-53
references: 16084689
references: Hypertension. 1992 Nov;20(5):612-9
references: 1428112
references: Nat Rev Endocrinol. 2009 May;5(5):253-61
references: 19444258
references: J Clin Sleep Med. 2008 Dec 15;4(6):538-42
references: 19110882
references: J Neurosci. 2000 Apr 15;20(8):2817-24
references: 10751433
references: Proc Natl Acad Sci U S A. 2004 Mar 9;101(10):3632-7
references: 14978286
references: Ageing Res Rev. 2002 Feb;1(1):61-77
references: 12039449
references: Am J Physiol Cell Physiol. 2010 Jun;298(6):C1594-602
references: 20357179
references: J Alzheimers Dis. 2012;29(4):783-91
references: 22337827
references: Am J Respir Crit Care Med. 2004 Feb 1;169(3):348-53
references: 14551167
references: J Neurol Sci. 2007 Jun 15;257(1-2):62-6
references: 17320909
references: Free Radic Biol Med. 2003 Aug 1;35(3):226-35
references: 12885585
references: Am J Respir Crit Care Med. 2002 Apr 1;165(7):859-60
references: 11934709
references: Proc Natl Acad Sci U S A. 1996 Feb 20;93(4):1710-5
references: 8643694
references: Proc Natl Acad Sci U S A. 2012 Apr 17;109(16):6277-82
references: 22451915
references: Sleep. 1999 Sep 15;22(6):749-55
references: 10505820
references: Hypertension. 1992 Nov;20(5):601-5
references: 1428110
references: Sleep Breath. 2012 Mar;16(1):123-33
references: 21213062
references: J Neurosci. 2007 Sep 12;27(37):10060-71
references: 17855620
references: Biochemistry (Mosc). 2007 May;72(5):471-8
references: 17573700
references: Sleep Breath. 2013 Mar;17(1):33-8
references: 22411171
references: Eur Respir J. 2008 Aug;32(2):399-404
references: 18448490
references: Neurology. 1999 Mar 10;52(4):786-91
references: 10078729
references: J Cereb Blood Flow Metab. 2006 Apr;26(4):449-55
references: 16094317
references: Neurosci Lett. 1998 Nov 27;257(2):77-80
references: 9865931
references: J Alzheimers Dis. 2004 Aug;6(4):355-66; discussion 443-9
references: 15345805
references: Adv Exp Med Biol. 2006;588:65-73
references: 17089880
references: Am J Respir Crit Care Med. 2007 Jan 15;175(2):190-5
references: 17068329
references: Int J Clin Pract Suppl. 2002 Jul;(129):59-64
references: 12166609
references: Sleep Disord. 2012;2012:251096
references: 23470865
references: J Neurosci. 2012 Apr 4;32(14):4878-86
references: 22492044
references: Sleep Med Rev. 2007 Apr;11(2):99-111
references: 17275370
references: Sleep. 1992 Dec;15(6 Suppl):S17-9
references: 1470802
references: Sleep. 1997 Sep;20(9):705-6
references: 9406321
references: Neuron. 1988 Oct;1(8):623-34
references: 2908446
references: Am J Cardiol. 2007 Aug 6;100(3A):17J-24J
references: 17666193
references: J Appl Physiol (1985). 1997 Jul;83(1):95-101
references: 9216950
references: Neurosci Res. 2001 Jul;40(3):245-54
references: 11448516
references: Respiration. 2011;82(5):409-17
references: 21311167
references: J Am Geriatr Soc. 2008 Nov;56(11):2076-81
references: 18795985
references: Exp Neurol. 1997 Sep;147(1):103-14
references: 9294407
references: J Neurol Sci. 1995 Aug;131(2):162-9
references: 7595642
references: J Nutr Health Aging. 2012 Oct;16(10):888-90
references: 23208027
references: Neurosci Lett. 2005 Feb 28;375(2):123-8
references: 15670654
references: Ann N Y Acad Sci. 2009 Oct;1177:169-77
references: 19845619
references: Sleep Breath. 2013 Mar;17(1):85-91
references: 22294346
references: J Biol Chem. 1994 Sep 23;269(38):23757-63
references: 8089148
references: Brain Res. 2007 Nov 7;1179:42-50
references: 17888415
references: Arch Neurol. 2009 Mar;66(3):336-42
references: 19273752
references: Sleep. 2004 Nov 1;27(7):1344-9
references: 15586787
references: J Neurobiol. 1998 Jul;36(1):64-80
references: 9658339
references: J Int Neuropsychol Soc. 2010 Nov;16(6):1077-88
references: 20735887
references: Neurology. 1994 Oct;44(10):1885-91
references: 7936242
references: Ann N Y Acad Sci. 2005 May;1042:203-9
references: 15965064
references: Neurology. 2004 Feb 10;62(3):491-3
references: 14872041
references: Neuroscience. 2002;115(1):201-11
references: 12401334
references: Sleep. 2010 Feb;33(2):235-41
references: 20175407
references: Neurobiol Aging. 2002 Sep-Oct;23(5):795-807
references: 12392783
references: Arch Neurol. 2003 Mar;60(3):337-41
references: 12633144
references: Laryngoscope. 1991 Dec;101(12 Pt 1):1318-22
references: 1766303
references: Clin Chest Med. 2003 Jun;24(2):249-59
references: 12800782
references: Circ Res. 1990 Jan;66(1):8-17
references: 2403863
references: Sleep Disord. 2011;2011:596879
references: 23470957
references: J Cardiovasc Pharmacol. 1985;7 Suppl 2:S94-8
references: 2409378
references: J Neurochem. 1999 Oct;73(4):1549-56
references: 10501200
references: J Biol Chem. 2007 Apr 13;282(15):10873-80
references: 17303576
references: Cytokine. 2000 Mar;12(3):246-52
references: 10704252
references: Sleep. 2008 Jul;31(7):967-77
references: 18652092
references: J Clin Neurosci. 2011 Nov;18(11):1454-7
references: 21917464
references: Lancet. 1994 Jul 2;344(8914):14-8
references: 7912295
references: Obes Rev. 2011 May;12(5):e426-37
references: 21348917
references: Front Biosci (Elite Ed). 2012 Jan 01;4:2007-21
references: 22202016
references: Chest. 2002 Oct;122(4):1162-7
references: 12377837
references: J Med Invest. 2006 Feb;53(1-2):134-9
references: 16538006
references: Ann Neurol. 2012 Jun;71(6):825-33
references: 22447734
references: Ann Neurol. 2005 Jan;57(1):98-103
references: 15562458
references: Sleep Breath. 2012 Dec;16(4):1033-40
references: 21948102
references: Neurochem Res. 2012 Apr;37(4):846-68
references: 22219130
references: Proc Natl Acad Sci U S A. 1997 Nov 25;94(24):13287-92
references: 9371838
references: J Int Neuropsychol Soc. 2000 Jan;6(1):86-99
references: 10761372
references: Arterioscler Thromb Vasc Biol. 2006 Apr;26(4):826-32
references: 16439707
references: Curr Alzheimer Res. 2008 Oct;5(5):438-47
references: 18855585
references: Sleep. 2002 Dec;25(8):850-5
references: 12489890
references: J Neurol Neurosurg Psychiatry. 2001 Sep;71(3):334-9
references: 11511706
references: Hypertension. 2008 Jan;51(1):99-104
references: 18025297
references: Brain. 1990 Feb;113 ( Pt 1):27-47
references: 2302536