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