title: Genetic diagnosis and prognosis of Alzheimer's disease: challenges and opportunities.
abstract: Alzheimer's disease (AD), the most common form of dementia in western societies, is a pathologically and clinically heterogeneous disease with a strong genetic component. The recent advances in high-throughput genome technologies allowing for the rapid analysis of millions of polymorphisms in thousands of subjects has significantly advanced our understanding of the genomic underpinnings of AD susceptibility. During the last 5 years, genome-wide association and whole-exome- and whole-genome sequencing studies have mapped more than 20 disease-associated loci, providing insights into the molecular pathways involved in AD pathogenesis and hinting at potential novel therapeutic targets. This review article summarizes the challenges and opportunities of when using genomic information for the diagnosis and prognosis of AD.
authors: Department of Neurology, Sergievsly Center, Taub Institute, Columbia University, 630 W 168th Street, Rm 19-308, New York, NY 10032, USA.
authors: Christiane
authors: C
authors: Reitz
mesh_terms: D000544:Alzheimer Disease / Q000175:diagnosis* / Q000453:epidemiology / Q000235:genetics* / Q000628:therapy; D015415:Biomarkers; D019295:Computational Biology; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing / Q000379:methods; D055106:Genome-Wide Association Study; D023281:Genomics / Q000379:methods; D006801:Humans; D011379:Prognosis
chemical_list: D015415:Biomarkers
keywords: Alzheimer’s disease; diagnosis; genomics; prognosis; therapy
references: Brain Res Rev. 2009 Oct;61(2):89-104
references: 19651157
references: BMJ. 1994 Sep 10;309(6955):636-8
references: 8086986
references: Nature. 2009 Oct 8;461(7265):747-53
references: 19812666
references: PLoS One. 2013 May 20;8(5):e64307
references: 23700469
references: J Atheroscler Thromb. 2011;18(4):274-81
references: 21173549
references: Neurology. 1996 Jan;46(1):149-54
references: 8559365
references: Nat Genet. 2011 May;43(5):436-41
references: 21460841
references: Nat Genet. 2013 Dec;45(12):1452-8
references: 24162737
references: Lancet Neurol. 2012 Dec;11(12):1048-56
references: 23137948
references: CMAJ. 2004 Oct 12;171(8):863-7
references: 15477624
references: Nat Neurosci. 2001 Sep;4(9):887-93
references: 11528419
references: J Neurol Neurosurg Psychiatry. 1996 Dec;61(6):580-3
references: 8971103
references: Nature. 1991 Feb 21;349(6311):704-6
references: 1671712
references: Am J Physiol Renal Physiol. 2002 Oct;283(4):F734-43
references: 12217865
references: Arch Neurol. 2006 May;63(5):693-9
references: 16682538
references: Neuron. 2013 Oct 16;80(2):385-401
references: 24055016
references: Neurobiol Aging. 2009 Aug;30(8):1254-64
references: 18078695
references: Dement Geriatr Cogn Disord. 2008;26(2):101-8
references: 18617739
references: Neurology. 1992 Feb;42(2):447-9
references: 1736183
references: Ann Neurol. 1996 Jan;39(1):62-70
references: 8572669
references: Cell. 1998 Sep 4;94(5):667-77
references: 9741631
references: J Neurol Neurosurg Psychiatry. 2007 Oct;78(10):1158-9
references: 17442758
references: Neurogenetics. 2007 Aug;8(3):179-88
references: 17387528
references: Trends Neurosci. 2011 Aug;34(8):430-42
references: 21696834
references: Lancet. 1993 Sep 18;342(8873):697-9
references: 8103819
references: Neurobiol Aging. 2014 Mar;35(3):726.e11-9
references: 24119542
references: Arch Neurol. 2005 Jun;62(6):975-80
references: 15956169
references: Sci Transl Med. 2014 Mar 19;6(228):228fs13
references: 24648338
references: Nat Genet. 2011 May;43(5):429-35
references: 21460840
references: Nat Genet. 2009 Oct;41(10):1088-93
references: 19734902
references: PLoS Genet. 2013;9(8):e1003685
references: 23990795
references: Neurobiol Aging. 2014 Jun;35(6):1510.e19-26
references: 24439484
references: Hypertension. 2013 Feb;61(2):319-26
references: 23232644
references: Nat Rev Immunol. 2003 Jun;3(6):445-53
references: 12776204
references: Neurology. 2013 Dec 3;81(23):2028-31
references: 24212387
references: Neurobiol Aging. 2013 Dec;34(12):2890.e1-5
references: 23870839
references: J Exp Med. 2003 Aug 18;198(4):669-75
references: 12925681
references: Science. 2009 Mar 13;323(5920):1473-7
references: 19286555
references: Lancet Neurol. 2006 Aug;5(8):655-60
references: 16857570
references: Alzheimers Res Ther. 2013 Oct 17;5(5):48
references: 24131566
references: Science. 1992 Apr 10;256(5054):184-5
references: 1566067
references: Alzheimers Res Ther. 2011 Jan 06;3(1):1
references: 21211070
references: Ann Neurol. 1999 Sep;46(3):412-6
references: 10482274
references: Dementia. 1996 Sep-Oct;7(5):251-5
references: 8872415
references: PLoS One. 2012;7(2):e31039
references: 22312439
references: Nature. 2014 Jan 23;505(7484):550-554
references: 24336208
references: Science. 1993 Aug 13;261(5123):921-3
references: 8346443
references: Biomark Med. 2010 Feb;4(1):3-14
references: 20383319
references: Mol Biol Cell. 1999 Aug;10(8):2687-702
references: 10436022
references: N Engl J Med. 2013 Apr 4;368(14):1326-34
references: 23550670
references: JAMA Neurol. 2013 Jan;70(1):133
references: 23318524
references: Eur J Hum Genet. 2009 Aug;17(8):1070-5
references: 19223933
references: Am Heart J. 2009 Jul;158(1):105-10
references: 19540399
references: Nat Genet. 1992 Aug;1(5):345-7
references: 1302033
references: Neurology. 2005 Aug 23;65(4):565-71
references: 16116117
references: JAMA. 1995 Apr 26;273(16):1274-8
references: 7646655
references: Nat Med. 1996 Aug;2(8):864-70
references: 8705854
references: Science. 1996 Oct 25;274(5287):536-9
references: 8928008
references: Alzheimers Dement. 2014 Oct;10(5 Suppl):S277-S283.e10
references: 24239249
references: Neurobiol Aging. 2012 Mar;33(3):437-56
references: 20594621
references: EMBO J. 2012 May 16;31(10):2261-74
references: 22505025
references: Hosp Pract (1995). 1997 Jul 15;32(7):51-5, 58-63, 67-9
references: 9227658
references: N Engl J Med. 2013 Oct 17;369(16):1564-5
references: 24131184
references: J Neurochem. 2008 Jul;106(2):793-804
references: 18429932
references: J Alzheimers Dis. 2011;26 Suppl 3:321-9
references: 21971471
references: Brain. 2006 Nov;129(Pt 11):2977-83
references: 16921174
references: J Leukoc Biol. 2010 Jun;87(6):1059-68
references: 20160140
references: Eur J Nucl Med Mol Imaging. 2012 Apr;39(4):621-31
references: 22252372
references: Neurology. 2009 Oct 13;73(15):1193-9
references: 19822868
references: N Engl J Med. 2013 Jan 10;368(2):107-16
references: 23150908
references: Lancet Neurol. 2011 May;10(5):424-35
references: 21481640
references: Am J Hum Genet. 2001 Jul;69(1):124-37
references: 11404818
references: Science. 1995 Aug 18;269(5226):973-7
references: 7638622
references: JAMA. 2013 Apr 10;309(14):1483-92
references: 23571587
references: Arch Neurol. 2011 Jan;68(1):99-106
references: 21220680
references: N Engl J Med. 2012 Aug 30;367(9):795-804
references: 22784036
references: Diabetes Care. 2013 Sep;36(9):2836-42
references: 23603917
references: Ann Neurol. 2008 Mar;63(3):377-87
references: 18300294
references: Arch Neurol. 1998 Jul;55(7):964-8
references: 9678314
references: Mol Neurodegener. 2013 Jun 21;8:19
references: 23800361
references: JAMA. 2010 May 12;303(18):1832-40
references: 20460622
references: Neurology. 2004 Jul 27;63(2):234-40
references: 15277614
references: Alzheimers Dement. 2010 Mar;6(2):158-94
references: 20298981
references: Am J Epidemiol. 2007 Jun 1;165(11):1231-8
references: 17431012
references: Hum Mutat. 2012 Sep;33(9):1340-4
references: 22581678
references: Biochem Pharmacol. 2014 Apr 15;88(4):426-49
references: 24275164
references: Ann Neurol. 2013 Dec;74(6):905-13
references: 24448836
references: Immunobiology. 2012 Feb;217(2):244-50
references: 21840620
references: Neurology. 1999 Apr 22;52(7):1397-403
references: 10227624
references: Neurobiol Aging. 2013 Oct;34(10):2443.e1-2
references: 23759145
references: J Int Med Res. 2011;39(2):522-7
references: 21672356
references: N Engl J Med. 2013 Jan 10;368(2):117-27
references: 23150934
references: Brain. 2008 May;131(Pt 5):1252-8
references: 18334538
references: Neurodegener Dis. 2008;5(5):268-76
references: 18309230
references: Int J Geriatr Psychiatry. 2009 Oct;24(10):1119-26
references: 19449451
references: Dement Geriatr Cogn Disord. 2009;27(5):458-64
references: 19420940
references: Neurobiol Aging. 2011 Jul;32(7):1207-18
references: 19660834
references: J Neurosci. 2006 Oct 4;26(40):10222-31
references: 17021177
references: Alzheimers Dement. 2013 Jul;9(4):438-44
references: 23809364
references: Neurology. 1999 Jul 22;53(2):321-31
references: 10430421
references: Nat Cell Biol. 2009 Dec;11(12):1399-410
references: 19915558
references: Hum Mol Genet. 2009 Oct 15;18(20):3987-96
references: 19608551
references: Neurology. 1996 Mar;46(3):673-7
references: 8618665
references: J Cell Sci. 2009 Jan 15;122(Pt 2):243-55
references: 19118217
references: JAMA. 1997 Mar 12;277(10):793-9
references: 9052708
references: Nature. 2008 Nov 6;456(7218):18-21
references: 18987709
references: Nat Genet. 2007 Feb;39(2):168-77
references: 17220890
references: Neurodegener Dis. 2008;5(3-4):186-9
references: 18322386
references: J Neurol. 1996 Jun;243(6):452-6
references: 8803817
references: Clin Investig (Lond). 2012 Oct 1;2(10):975-984
references: 23139856
references: Nat Genet. 2009 Oct;41(10):1094-9
references: 19734903
references: Nature. 1995 Jun 29;375(6534):754-60
references: 7596406
references: Mol Neurodegener. 2013 Jun 21;8:20
references: 23800368
references: Hum Mol Genet. 2009 Sep 15;18(18):3525-31
references: 19553258
references: Neurosci Lett. 2001 Apr 6;301(3):199-203
references: 11257432
references: J Biol Chem. 2008 Oct 31;283(44):29615-9
references: 18650430
references: Stroke. 2014 Feb;45(2):403-12
references: 24436238
references: Ann Neurol. 2004 Mar;55(3):306-19
references: 14991808