title: Metabolic profiling of Alzheimer's disease brains.
abstract: Alzheimer's disease (AD) is an irreversible, progressive brain disease and can be definitively diagnosed after death through an examination of senile plaques and neurofibrillary tangles in several brain regions. It is to be expected that changes in the concentration and/or localization of low-molecular-weight molecules are linked to the pathological changes that occur in AD, and determining their identity would provide valuable information regarding AD processes. Here, we propose definitive brain metabolic profiling using ultra-performance liquid chromatography coupled with electrospray time-of-flight mass spectrometry analysis. The acquired data were subjected to principal components analysis to differentiate the frontal and parietal lobes of the AD/Control groups. Significant differences in the levels of spermine and spermidine were identified using S-plot, mass spectra, databases and standards. Based on the investigation of the polyamine metabolite pathway, these data establish that the downstream metabolites of ornithine are increased, potentially implicating ornithine decarboxylase activity in AD pathology.
authors.affiliation: Laboratory of Analytical and Bio-Analytical Chemistry, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, Japan. kinoue@ushizuoka-ken.ac.jp
authors.forename: Koichi
authors.initials: K
authors.lastname: Inoue
authors.forename: Haruhito
authors.initials: H
authors.lastname: Tsutsui
authors.forename: Hiroyasu
authors.initials: H
authors.lastname: Akatsu
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Hashizume
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Matsukawa
authors.forename: Takayuki
authors.initials: T
authors.lastname: Yamamoto
authors.forename: Toshimasa
authors.initials: T
authors.lastname: Toyo'oka
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism*; D015317:Biogenic Polyamines / Q000378:metabolism*; D001921:Brain / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D055442:Metabolome; D009952:Ornithine / Q000378:metabolism*; D009955:Ornithine Decarboxylase / Q000378:metabolism*
chemical_list: D015317:Biogenic Polyamines; D009952:Ornithine; D009955:Ornithine Decarboxylase
references.citation: Anal Bioanal Chem. 2011 Jul;401(1):89-101
references.pmid: 21437774
references.citation: Anal Chem. 2009 Feb 1;81(3):1121-9
references.pmid: 19125563
references.citation: Acta Neuropathol. 1991;82(4):239-59
references.pmid: 1759558
references.citation: Alzheimers Dement. 2012 Jul;8(4):312-36
references.pmid: 22748938
references.citation: Immun Ageing. 2012 Sep 17;9(1):20
references.pmid: 22985434
references.citation: J Neurosci. 2011 Aug 3;31(31):11328-37
references.pmid: 21813692
references.citation: Neurology. 2012 Feb 14;78(7):468-76
references.pmid: 22302554
references.citation: N Engl J Med. 2012 Aug 30;367(9):795-804
references.pmid: 22784036
references.citation: J Lipid Res. 2012 Mar;53(3):567-576
references.pmid: 22203775
references.citation: Neurology. 2010 Jul 13;75(2):143-51
references.pmid: 20625167
references.citation: Electrophoresis. 2009 Apr;30(7):1235-9
references.pmid: 19288586
references.citation: N Engl J Med. 2003 Apr 3;348(14):1333-41
references.pmid: 12672860
references.citation: Arch Med Res. 2012 Nov;43(8):622-31
references.pmid: 23142261
references.citation: Can J Neurol Sci. 2012 Nov;39(6):712-28
references.pmid: 23227576
references.citation: Biomark Med. 2012 Aug;6(4):377-89
references.pmid: 22917140
references.citation: Neurology. 1991 Apr;41(4):479-86
references.pmid: 2011243
references.citation: J Neurochem. 2002 May;81(4):765-79
references.pmid: 12065636
references.citation: Neurology. 2011 Jan 18;76(3):280-6
references.pmid: 21178097
references.citation: Curr Opin Neurobiol. 2012 Jun;22(3):559-63
references.pmid: 21962484
references.citation: J Neurosci. 2013 Mar 27;33(13):5553-63
references.pmid: 23536070
references.citation: Int J Biochem Cell Biol. 2010 Jan;42(1):39-51
references.pmid: 19643201
references.citation: Curr Neurovasc Res. 2005 Jul;2(3):213-23
references.pmid: 16181115
references.citation: Stain Technol. 1988 Jul;63(4):197-200
references.pmid: 2464205
references.citation: Alzheimers Dement. 2011 May;7(3):309-17
references.pmid: 21075060
references.citation: Prog Neuropsychopharmacol Biol Psychiatry. 1998 Jan;22(1):35-64
references.pmid: 9533166
references.citation: J Chromatogr A. 2008 Sep 26;1205(1-2):94-102
references.pmid: 18755466
references.citation: J Neurol Neurosurg Psychiatry. 1985 Nov;48(11):1085-90
references.pmid: 4078573
references.citation: Clin Biochem. 2010 Aug;43(12):992-7
references.pmid: 20457143
references.citation: Nat Rev Neurol. 2013 Feb;9(2):106-18
references.pmid: 23296339
references.citation: Biochem J. 2011 Aug 15;438(1):165-75
references.pmid: 21639855
references.citation: Mol Chem Neuropathol. 1992 Jun;16(3):241-71
references.pmid: 1358085
references.citation: J Neurosci. 2012 Dec 12;32(50):18227-33
references.pmid: 23238736
references.citation: Clin Chim Acta. 2011 Jan 14;412(1-2):98-106
references.pmid: 20869356
references.citation: PLoS One. 2011;6(7):e21643
references.pmid: 21779331
references.citation: Lancet. 1991 May 11;337(8750):1158-9
references.pmid: 1674030
references.citation: J Alzheimers Dis. 2013;36(2):311-20
references.pmid: 23609763
references.citation: Dement Geriatr Cogn Disord. 2012;33(1):1-5
references.pmid: 22343824
references.citation: Neurobiol Aging. 2013 Apr;34(4):1007-17
references.pmid: 23159550
references.citation: Anal Chem. 2013 Feb 5;85(3):1803-11
references.pmid: 23252551
references.citation: Mass Spectrom Rev. 2012 Jan-Feb;31(1):70-95
references.pmid: 21538458
references.citation: Neurology. 2013 Jan 22;80(4):359-65
references.pmid: 23255822
references.citation: Ann Epidemiol. 2012 Dec;22(12):868-75
references.pmid: 23102709
references.citation: Biomark Med. 2012 Aug;6(4):455-76
references.pmid: 22917147
references.citation: J Pharm Biomed Anal. 2010 Mar 11;51(4):812-23
references.pmid: 19879709
references.citation: J Biol Chem. 2012 Jan 20;287(4):2678-88
references.pmid: 22134919
references.citation: Biol Psychiatry. 2013 Sep 1;74(5):340-7
references.pmid: 23290495
references.citation: Mol Pharmacol. 1994 May;45(5):803-9
references.pmid: 8190097
references.citation: Neurosci Lett. 1999 Mar 19;263(1):17-20
references.pmid: 10218900
references.citation: Alzheimers Res Ther. 2012 Aug 27;4(4):32
references.pmid: 22929359
references.citation: J Proteome Res. 2010 Aug 6;9(8):3912-22
references.pmid: 20557141
references.citation: J Neurosci Res. 2001 Mar 1;63(5):395-401
references.pmid: 11223914
references.citation: Brain Nerve. 2010 Oct;62(10):1043-52
references.pmid: 20940503
references.citation: Clin Chim Acta. 2011 May 12;412(11-12):861-72
references.pmid: 21185819
references.citation: Int J Geriatr Psychiatry. 1999 Jan;14(1):3-47
references.pmid: 10029935
references.citation: PLoS One. 2012;7(2):e31501
references.pmid: 22359596
references.citation: Acta Morphol Acad Sci Hung. 1971;19(1):1-8
references.pmid: 4107507
references.citation: J Alzheimers Dis. 2011;26(4):745-53
references.pmid: 21694449
references.citation: J Phys Condens Matter. 2012 Jun 20;24(24):244102
references.pmid: 22595372
references.citation: Brain Pathol. 2010 May;20(3):571-80
references.pmid: 19832840
references.citation: PLoS One. 2011;6(10):e24777
references.pmid: 22046234
references.citation: Biomark Med. 2012 Aug;6(4):477-95
references.pmid: 22917148
references.citation: J Chromatogr A. 2011 Oct 21;1218(42):7713-22
references.pmid: 21872257
references.citation: J Alzheimers Dis. 2013;35(3):509-24
references.pmid: 23478305
references.citation: Cold Spring Harb Perspect Med. 2012 Sep 01;2(9):a006387
references.pmid: 22951439
references.citation: J Sep Sci. 2011 Mar;34(6):659-66
references.pmid: 21284082