title: Alzheimer's and seizures: interleukin-18, indoleamine 2,3-dioxygenase and quinolinic Acid.
abstract: Emergent seizures are common in Alzheimer's disease (AD), although the mechanisms mediating this are unknown. It is proposed that stress induced interleukin-18 (IL-18), via interferon-gamma (IFNy) and independently, increases indoleamine 2,3-dioxygenase (IDO) and subsequent quinolinic acid (QA) in microglia. QA increases seizures and concurrently contributes to neuronal loss via excitotoxicity. The ApoE4 allele interacts with IL-18 polymorphisms to increase the risk of AD, and seems likely to potentiate the emergence of seizures. Concurrent changes in IDO and the kynurenine pathways at the blood-brain-barrier (BBB) have implications for treatment, including in the efficacy of different anti-hypertensives. Melatonin is proposed to inhibit these overlapping excitotoxic and neurodegenerative processes, and would be a useful adjunctive treatment.
authors.affiliation: CRC, Rm 1/2, 1229 Dumbarton Road, Glasgow, Scotland, U.K.
authors.forename: G
authors.initials: G
authors.lastname: Anderson
authors.forename: Jo
authors.initials: J
authors.lastname: Ojala
references.citation: J Pineal Res. 2009 Oct;47(3):211-20
references.pmid: 19627456
references.citation: J Neurochem. 2010 Jan;112(1):66-76
references.pmid: 19818105
references.citation: Brain Res. 2004 Aug 20;1018(1):48-54
references.pmid: 15262204
references.citation: Anticancer Res. 2002 Mar-Apr;22(2A):931-6
references.pmid: 12014674
references.citation: Inflammation. 2003 Jun;27(3):147-59
references.pmid: 12875368
references.citation: Neuron. 2007 Sep 6;55(5):697-711
references.pmid: 17785178
references.citation: Brain Res. 2009 Feb 9;1253:169-75
references.pmid: 19073159
references.citation: J Neurochem. 2008 May;105(4):1346-57
references.pmid: 18221377
references.citation: Trends Mol Med. 2009 Feb;15(2):41-9
references.pmid: 19162548
references.citation: J Pineal Res. 2009 Apr;46(3):262-7
references.pmid: 19196437
references.citation: Eur J Neurosci. 2009 Feb;29(3):529-38
references.pmid: 19187269
references.citation: J Pineal Res. 2009 Mar;46(2):188-98
references.pmid: 19054298
references.citation: Neurol Res. 2009 Nov;31(9):989-95
references.pmid: 19138464
references.citation: Cell Signal. 2009 Feb;21(2):264-73
references.pmid: 19007880
references.citation: Neurobiol Aging. 2009 Feb;30(2):198-209
references.pmid: 17658666
references.citation: Arch Neurol. 2009 Apr;66(4):435-40
references.pmid: 19204149
references.citation: J Neurosci. 2009 Apr 1;29(13):4200-9
references.pmid: 19339614
references.citation: J Pineal Res. 2008 Sep;45(2):157-65
references.pmid: 18298462
references.citation: Circulation. 2005 Sep 20;112(12):1798-805
references.pmid: 16172287
references.citation: J Neuroimmunol. 2008 Dec 15;205(1-2):86-93
references.pmid: 18947885
references.citation: Neuron. 2010 Jan 14;65(1):4-6
references.pmid: 20152108
references.citation: J Neurochem. 2009 Aug;110(3):791-800
references.pmid: 19457071
references.citation: Neuropsychopharmacology. 2007 Feb;32(2):284-8
references.pmid: 16710316
references.citation: J Immunol. 2003 May 15;170(10):5281-94
references.pmid: 12734378
references.citation: Neurology. 2000 Aug 8;55(3):435-7
references.pmid: 10932283
references.citation: Antioxid Redox Signal. 2007 Sep;9(9):1485-97
references.pmid: 17638545
references.citation: Brain Res. 2009 Apr 6;1264:98-103
references.pmid: 19368815
references.citation: Arch Neurol. 2009 Aug;66(8):992-7
references.pmid: 19667221
references.citation: Br J Nutr. 2008 Jun;99(6):1199-207
references.pmid: 18081942
references.citation: Brain Behav Immun. 2009 May;23(4):507-17
references.pmid: 19486646
references.citation: Neurochem Res. 2008 Sep;33(9):1749-58
references.pmid: 18307036
references.citation: Blood. 2009 Oct 8;114(15):3235-43
references.pmid: 19625705
references.citation: J Med Invest. 2005 Nov;52 Suppl:236-9
references.pmid: 16366505
references.citation: J Neurosci Res. 2010 Jun;88(8):1615-31
references.pmid: 20127816
references.citation: J Pineal Res. 2007 Oct;43(3):232-8
references.pmid: 17803519
references.citation: Exp Neurol. 2010 Jun;223(2):322-5
references.pmid: 19782073
references.citation: Cytokine Growth Factor Rev. 1998 Jun;9(2):109-16
references.pmid: 9754705
references.citation: Med Hypotheses. 2001 Aug;57(2):156-60
references.pmid: 11461164
references.citation: Cell Mol Life Sci. 2010 Feb;67(3):353-68
references.pmid: 19826765
references.citation: Brain Res Rev. 2008 Jun;58(1):85-95
references.pmid: 18295340