title: Biomarkers in Alzheimer's disease: past, present and future.
abstract: Epidemiological and molecular studies suggest that Alzheimer's disease (AD) has multiple etiologies including genetic mutations, genetic variations affecting susceptibility and environmental factors. These aspects can promote the formation and accumulation of insoluble amyloid-beta and hyperphosphorylated tau. Since the disease is multifactorial and clinical diagnosis is highly exclusive, the need for a sensitive, specific and reliable biomarker is crucial. The concept of a biomarker implies sensitivity and specificity relative to the condition being considered. For clinical practice, AD diagnosis has been based on adherence to clinical criteria such as the NINCDS/ADRDA and DSM-IV. A more recent set of diagnostic criteria proposed incorporates imaging findings into the diagnosis of AD. In this article, we consider the most studied candidates or group of candidates for AD biomarkers, including pathological processes and proteins (amyloid-beta, tau, oxidative stress, mitochondrial/metabolic changes and cell-cycle processes), or autoantibodies thereto, as well as genetic factors.
authors.affiliation: University Hospitals, Case Medical Center and University Memory and Cognitive Center, Case Western Reserve University, Cleveland, OH, USA.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Gustaw-Rothenberg
authors.forename: Alan
authors.initials: A
authors.lastname: Lerner
authors.forename: David J
authors.initials: DJ
authors.lastname: Bonda
authors.forename: Hyoung-gon
authors.initials: HG
authors.lastname: Lee
authors.forename: Xiongwei
authors.initials: X
authors.lastname: Zhu
authors.forename: George
authors.initials: G
authors.lastname: Perry
authors.forename: Mark A
authors.initials: MA
authors.lastname: Smith
mesh_terms: D000544:Alzheimer Disease / Q000175:diagnosis* / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000378:metabolism; D001057:Apolipoproteins E / Q000235:genetics; D015415:Biomarkers / Q000378:metabolism*; D002453:Cell Cycle; D005819:Genetic Markers; D006801:Humans; D010084:Oxidation-Reduction; D016875:tau Proteins / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D001057:Apolipoproteins E; D015415:Biomarkers; D005819:Genetic Markers; C054369:MAPT protein, human; D016875:tau Proteins
references.citation: J Neural Transm (Vienna). 2001;108(12):1397-415
references.pmid: 11810404
references.citation: J Alzheimers Dis. 2001 Feb;3(1):75-80
references.pmid: 12214075
references.citation: Psychopharmacol Bull. 1988;24(4):627-8
references.pmid: 3249763
references.citation: EMBO J. 1994 Mar 1;13(5):1114-22
references.pmid: 8131745
references.citation: J Biol Chem. 1984 Apr 25;259(8):5301-5
references.pmid: 6425287
references.citation: J Cell Biol. 1998 Oct 19;143(2):457-67
references.pmid: 9786955
references.citation: Am J Pathol. 2009 Mar;174(3):891-7
references.pmid: 19164506
references.citation: J Psychiatr Res. 1975 Nov;12(3):189-98
references.pmid: 1202204
references.citation: Biochim Biophys Acta. 2007 Apr;1772(4):467-72
references.pmid: 17095196
references.citation: Nat Med. 2007 Nov;13(11):1359-62
references.pmid: 17934472
references.citation: J Neurochem. 2008 Aug;106(3):1350-6
references.pmid: 18485104
references.citation: J Biol Chem. 2009 Feb 20;284(8):4749-53
references.pmid: 18845536
references.citation: Nature. 1999 Jul 8;400(6740):173-7
references.pmid: 10408445
references.citation: Curr Alzheimer Res. 2006 Feb;3(1):75-80
references.pmid: 16472207
references.citation: Ann Med. 2008;40(8):562-83
references.pmid: 18608129
references.citation: J Biol Chem. 1996 Dec 20;271(51):32916-22
references.pmid: 8955133
references.citation: Acta Neuropathol. 1984;62(3):167-77
references.pmid: 6538056
references.citation: Med Hypotheses. 1999 Jun;52(6):525-7
references.pmid: 10459833
references.citation: Neuroimage. 2009 Apr 15;45(3):645-55
references.pmid: 19280686
references.citation: Science. 1996 Dec 6;274(5293):1710-3
references.pmid: 8939861
references.citation: JAMA. 1997 Oct 22-29;278(16):1349-56
references.pmid: 9343467
references.citation: Aging (Milano). 1997 Jun;9(3):175-9
references.pmid: 9258375
references.citation: J Neurochem. 2008 Sep;106(5):2218-23
references.pmid: 18624923
references.citation: Brain. 2004 Jan;127(Pt 1):133-42
references.pmid: 14570818
references.citation: Exp Gerontol. 2010 Jan;45(1):47-52
references.pmid: 19819324
references.citation: Lancet Neurol. 2007 Aug;6(8):734-46
references.pmid: 17616482
references.citation: Dialogues Clin Neurosci. 2009;11(2):141-57
references.pmid: 19585950
references.citation: Mech Ageing Dev. 2001 Dec;123(1):39-46
references.pmid: 11640950
references.citation: Proc Natl Acad Sci U S A. 1997 Sep 2;94(18):9705-10
references.pmid: 9275188
references.citation: Proc Natl Acad Sci U S A. 1993 Jun 1;90(11):5066-70
references.pmid: 8506352
references.citation: Prog Neurobiol. 2003 Dec;71(5):385-400
references.pmid: 14757117
references.citation: DNA Cell Biol. 2001 Nov;20(11):731-6
references.pmid: 11788051
references.citation: J Neurosci. 2001 May 1;21(9):3017-23
references.pmid: 11312286
references.citation: Science. 2002 Jul 19;297(5580):353-6
references.pmid: 12130773
references.citation: Neuroreport. 1993 Jan;4(1):69-72
references.pmid: 8453039
references.citation: Neurobiol Aging. 2004 Sep;25(8):1023-32
references.pmid: 15212827
references.citation: Neuroscience. 2000;99(2):305-16
references.pmid: 10938436
references.citation: Free Radic Biol Med. 1997;23(1):134-47
references.pmid: 9165306
references.citation: Proc Natl Acad Sci U S A. 1994 Jul 19;91(15):7104-8
references.pmid: 8041753
references.citation: Brain. 2009 Aug;132(Pt 8):2036-47
references.pmid: 19439419
references.citation: Biochim Biophys Acta. 2007 Apr;1772(4):494-502
references.pmid: 17142016
references.citation: Science. 1996 Dec 6;274(5293):1664-72
references.pmid: 8939848
references.citation: J Neurochem. 2009 May;109 Suppl 1:153-9
references.pmid: 19393022
references.citation: Ann Intern Med. 2003 Mar 4;138(5):400-10
references.pmid: 12614093
references.citation: J Neurochem. 2000 Jan;74(1):125-33
references.pmid: 10617113
references.citation: Lancet Neurol. 2006 Dec;5(12):1000-1; author reply 1002-3
references.pmid: 17110278
references.citation: Am J Pathol. 2003 May;162(5):1623-7
references.pmid: 12707046
references.citation: Nature. 1999 Apr 8;398(6727):522-5
references.pmid: 10206646
references.citation: J Alzheimers Dis. 2008 Aug;14(4):377-83
references.pmid: 18688087
references.citation: Int Rev Neurobiol. 1998;42:1-54
references.pmid: 9476170
references.citation: J Alzheimers Dis. 2002 Jun;4(3):249-54
references.pmid: 12226545
references.citation: J Immunol. 1993 Jun 15;150(12):5566-75
references.pmid: 8515076
references.citation: J Biol Chem. 1999 Jul 2;274(27):19011-6
references.pmid: 10383401
references.citation: NeuroRx. 2004 Apr;1(2):213-25
references.pmid: 15717022
references.citation: J Neurosci. 2003 Apr 1;23(7):2557-63
references.pmid: 12684440
references.citation: Annu Rev Cell Dev Biol. 1998;14:59-88
references.pmid: 9891778
references.citation: JAMA. 1989 Nov 10;262(18):2551-6
references.pmid: 2810583
references.citation: Science. 1989 Mar 17;243(4897):1488-90
references.pmid: 2928783
references.citation: Dement Geriatr Cogn Disord. 2008;26(5):440-4
references.pmid: 18957849
references.citation: J Cell Biol. 1996 Feb;132(3):413-25
references.pmid: 8636218
references.citation: Alzheimer Dis Assoc Disord. 1992 Winter;6(4):197-200
references.pmid: 1290622
references.citation: Am J Pathol. 1999 Jul;155(1):135-44
references.pmid: 10393846
references.citation: Neuromolecular Med. 2008;10(3):195-207
references.pmid: 18543125
references.citation: Lancet Neurol. 2004 Apr;3(4):219-26
references.pmid: 15039034
references.citation: Curr Opin Genet Dev. 1999 Feb;9(1):15-21
references.pmid: 10072352
references.citation: J Alzheimers Dis. 2004 Apr;6(2):137-45
references.pmid: 15096697
references.citation: J Neurosci. 1993 Jun;13(6):2540-50
references.pmid: 8501520
references.citation: Exp Neurol. 1994 Apr;126(2):185-94
references.pmid: 7925819
references.citation: J Neurosci Res. 2000 Jul 15;61(2):128-33
references.pmid: 10878584
references.citation: Neurobiol Aging. 2000 Nov-Dec;21(6):807-13
references.pmid: 11124424
references.citation: J Neurosci. 1998 Jun 15;18(12):4451-60
references.pmid: 9614222
references.citation: J Biol Chem. 2000 Feb 25;275(8):5395-9
references.pmid: 10681514
references.citation: BMC Neurosci. 2004 Jun 08;5:21
references.pmid: 15186505
references.citation: Proc Natl Acad Sci U S A. 1986 Jul;83(13):4913-7
references.pmid: 3088567
references.citation: J Neurobiol. 1998 Sep 15;36(4):455-67
references.pmid: 9740019
references.citation: J Biol Chem. 1996 Sep 13;271(37):22908-14
references.pmid: 8798471
references.citation: J Neuroinflammation. 2005 Jun 20;2:15
references.pmid: 15967035
references.citation: J Neurochem. 1992 May;58(5):1667-75
references.pmid: 1560225
references.citation: Mol Hum Reprod. 1997 Feb;3(2):83-90
references.pmid: 9239713
references.citation: Neurobiol Aging. 1999 May-Jun;20(3):271-8
references.pmid: 10588574
references.citation: Nature. 1999 Apr 8;398(6727):525-9
references.pmid: 10206647
references.citation: Neurology. 1984 Jul;34(7):939-44
references.pmid: 6610841
references.citation: FEBS Lett. 1992 Aug 17;308(2):218-24
references.pmid: 1323485
references.citation: Genet Epidemiol. 1994;11(6):539-51
references.pmid: 7713394
references.citation: FEBS Lett. 1993 Dec 28;336(3):417-24
references.pmid: 8282104
references.citation: J Neurosci. 1998 Apr 15;18(8):2801-7
references.pmid: 9525997
references.citation: Neurobiol Aging. 2011 Jul;32(7):1207-18
references.pmid: 19660834
references.citation: Curr Alzheimer Res. 2009 Aug;6(4):347-61
references.pmid: 19689234
references.citation: Biotech Histochem. 1996 Mar;71(2):66-70
references.pmid: 9138532
references.citation: Nat Med. 1996 Jul;2(7):783-7
references.pmid: 8673924
references.citation: Crit Rev Neurobiol. 1996;10(2):205-38
references.pmid: 8971130
references.citation: Acta Neuropathol. 2001 Apr;101(4):305-10
references.pmid: 11355301
references.citation: Trends Mol Med. 2005 Apr;11(4):164-9
references.pmid: 15823754
references.citation: Exp Gerontol. 2002 Jul;37(7):943-8
references.pmid: 12086704
references.citation: J Neurosci. 1999 Oct 15;19(20):8747-56
references.pmid: 10516294
references.citation: CNS Neurol Disord Drug Targets. 2008 Feb;7(1):3-10
references.pmid: 18289026
references.citation: PLoS One. 2009 Aug 07;4(8):e6501
references.pmid: 19668339
references.citation: Subcell Biochem. 2005;38:255-72
references.pmid: 15709483
references.citation: J Neurochem. 1998 Jan;70(1):1-14
references.pmid: 9422341
references.citation: Nature. 1997 May 15;387(6630):288-92
references.pmid: 9153393
references.citation: J Neurol Neurosurg Psychiatry. 2000 Oct;69(4):565-6
references.pmid: 11183042
references.citation: Trends Neurosci. 1995 Apr;18(4):172-6
references.pmid: 7778188
references.citation: Neurosignals. 2002 Sep-Oct;11(5):270-81
references.pmid: 12566928
references.citation: Science. 1988 Jun 3;240(4857):1285-93
references.pmid: 3287615
references.citation: Biochem Biophys Res Commun. 1990 Sep 14;171(2):690-6
references.pmid: 2403357
references.citation: Neuroscience. 1995 Sep;68(1):5-18
references.pmid: 7477934
references.citation: Neurology. 2001 Sep 11;57(5):801-5
references.pmid: 11552007
references.citation: Nat Med. 2007 Sep;13(9):1029-31
references.pmid: 17694066
references.citation: Neuroscience. 1999;91(1):1-5
references.pmid: 10336054
references.citation: Acta Neuropathol. 2006 Jun;111(6):503-9
references.pmid: 16718346