The genetics of Alzheimer's disease

Clinical Interventions in Aging

Volumn 9, Issue , 2014, Pages 535-551

  Bagyinszky, Eva ^a   Youn, Young Chul ^b   An, Seong Soo A ^a   Kim, Sangyun ^c  

^a Gachon University   (South Korea)

^b Chung Ang University College of Medicine   (South Korea)

^c Seoul National University Bundang Hospital   (South Korea)

Author keywords

Amyloid precursor protein; APOE; Dementia; Diagnosis; Genetic testing; Mutation; Presenilin 1; Presenilin 2

Indexed keywords

ADAM10 ENDOPEPTIDASE; AMYLOID PRECURSOR PROTEIN; APOLIPOPROTEIN E4; CD33 ANTIGEN; CLUSTERIN; COMPLEMENT COMPONENT C3B RECEPTOR; ENDONUCLEASE; LOW DENSITY LIPOPROTEIN RECEPTOR RELATED PROTEIN 6; PRESENILIN 1; PRESENILIN 2; SINGLE STRANDED DNA; APP PROTEIN, HUMAN; PSEN2 PROTEIN, HUMAN;

ABCA7 GENE; ADAM10 GENE; ALZHEIMER DISEASE; AMYLOID PRECURSOR PROTEIN GENE; APOLIPOPROTEIN E4 GENE; BIN1 GENE; CD33 GENE; CLUSTERIN GENE; COMPLEMENT RECEPTOR 1 GENE; CONFORMATIONAL TRANSITION; CTNNA3 GENE; DNA CONFORMATION; GENE; GENE IDENTIFICATION; GENE MUTATION; GENETIC ASSOCIATION; GENETIC RISK; GENOTYPE; HUMAN; LRP6 GENE; MOLECULAR PATHOLOGY; MUTATIONAL ANALYSIS; NONHUMAN; ONSET AGE; PHOSPHATIDYLINOSITOL BINDING CLATHRIN ASSEMBLY GENE; PRESENILIN 1 GENE; PRESENILIN 2 GENE; REVIEW; RISK FACTOR; SEQUENCE ANALYSIS; SORTILIN RELATED RECEPTOR GENE; TRIGGERING RECEPTOR EXPRESSED ON MYELOID CELLS GENE; AGE; AGED; GENETIC POLYMORPHISM; GENETIC PREDISPOSITION; GENETIC SCREENING; GENETICS; MIDDLE AGED;

AGE FACTORS; AGED; ALZHEIMER DISEASE; AMYLOID BETA-PROTEIN PRECURSOR; GENETIC PREDISPOSITION TO DISEASE; GENETIC TESTING; HUMANS; MIDDLE AGED; POLYMORPHISM, GENETIC; PRESENILIN-1; PRESENILIN-2;

EID: 84897476030     PISSN: 11769092     EISSN: 11781998     Source Type: Journal    
DOI: 10.2147/CIA.S51571     Document Type: Review

References (199)

1. Ertekin-Taner N. Genetics of Alzheimer's disease: a centennial review. Neurol Clin. 2007;25(12):611-617.
2. Reitz C, Mayeux R. Use of genetic variation as biomarkers for Alzheimer's disease. Ann N Y Acad Sci. 2009;1180:75-96.
3. Brickell KL, Leverenz JB, Steinbart EJ, etal. Clinicopathological concordance and discordance in three monozygotic twin pairs with familial Alzheimer's disease. J Neurol Neurosurg Psychiatry. 2007;78(10):1050-1055.
4. Meyer JM, Breitner JC. Multiple threshold model for the onset of Alzheimer's disease in the NAS-NRC twin panel. Am J Med Genet. 1998;81(1):92-97.
5. Bird DT. Genetic aspects of Alzheimer disease. Genet Med. 2008;10(4): 231-239.
6. Sorbi S, Forleo P, Tedde A, etal. Genetic risk factors in familial Alzheimer's disease. Mech Ageing Dev. 2001;122(16):1951-1960.
7. Schellenberg GD, Anderson L, O'dahl S, etal. APP717, APP693, and PRIP gene mutations are rare in Alzheimer disease. Am J Med Genet. 1991;49(3):511-517.
8. Tanzi RE, Vaula G, Romano DM, etal. Assessment of amyloid beta-protein precursor gene mutations in a large set of familial and sporadic Alzheimer disease cases. Am J Med Genet. 1992;51(2):273-282.
9. Bertram L, Tanzi RE. The genetic epidemiology of neurodegenerative disease. J Clin Investig. 2005;115(6):1449-1457.
10. Rademakers R, Cruts M, Van Broeckhoven C. Genetics of early-onset Alzheimer dementia. ScientificWorldJournal. 2003;3:497-519.
11. Prasher VP, Farrer MJ, Kessling AM, etal. Molecular mapping of Alzheimer-type dementia in Down's syndrome. Ann Neurolol. 1998;43(3):380-383.
12. König G, Mönning U, Czech C, etal. Identification and differential expression of a novel alternative splice isoform of the beta A4 amyloid precursor protein (APP) mRNA in leukocytes and brain microglial cells. J Biol Chem. 1992;267(15):10804-10809.
13. De Jonghe C, Esselens C, Kumar-Singh S, etal. Pathogenic APP mutations near the gamma-secretase cleavage site differentially affect Abeta secretion and APP C-terminal fragment stability. Hum Mol Genet. 2001;10(16):1665-1671.
14. Cruts M, Theuns J, Van Broeckhoven C. Locus-specific mutation databases for neurodegenerative brain diseases. Hum Mutat. 2012;33(9):1340-1344.
15. Mullan M, Crawford F, Axelman K, etal. A pathogenic mutation for probable Alzheimer's disease in the APP gene at the N-terminus of beta-amyloid. Nat Genet. 1992;1(5):345-347.
16. Tomiyama T, Nagata T, Shimada H, etal. A new amyloid beta variant favoring oligomerization in Alzheimer's-type dementia. Ann Neurol. 2008;63(3):377-387.
17. Roks G, Van Harskamp F, De Koning I, etal. Presentation of amyloidosis in carriers of the codon 692mutation in the amyloid precursor protein gene (APP692). Brain. 2000;123(Pt 10):2130-2140.
18. Golaz J, Charnay Y, Vallet P, Bouras C. [Alzheimer's disease and Down's syndrome. Some recent etiopathogenic data.] Encephale. 1991;17(1):29-31. French [with English abstract].
19. Cruts M, Hendriks L, Van Broeckhoven C. The presenilin genes: a new gene family involved in Alzheimer disease pathology. Hum Mol Genet. 1996;5 Spec No:1449-1455.
20. Wolfe MS, Xia W, Ostaszewski BL, Diehl TS, Kimberly WT, Selkoe DJ. Two transmembrane aspartates in presenilin-1 required for presenilin endoproteolysis and gamma-secretase activity. Nature. 1999;398(6727):513-517.
21. Campion D, Dumanchin C, Hannequin D, etal. Early-onset autosomal dominant Alzheimer disease: prevalence, genetic heterogeneity, and mutation spectrum. Am J Hum Genet. 1999;65(3):664-670.
22. Sleegers K, Roks G, Theuns J, etal. Familial clustering and genetic risk for dementia in a genetically isolated Dutch population. Brain. 2004;127(7):1641-1649.
23. Bekris LM, Yu CE, Bird TD, Tsuang DW. Genetics of Alzheimer Disease. J Geriatr Psychiatry Neurol. 2010;23(4):213-227.
24. Levy-Lahad E, Wasco W, Poorkaj P, etal. Candidate gene for the chromosome 1 familial Alzheimer's disease locus. Science. 1995;269(5226):973-977.
25. Rogaev EI, Sherrington R, Rogaeva EA, etal. Familial Alzheimer's disease in kindreds with missense mutations in a gene on chromosome 1 related to the Alzheimer's disease type 3 gene. Nature. 1995;376(6543):775-778.
26. Kamimura K, Tanahashi H, Yamanaka H, Takahashi K, Asada T, Tabira T. Familial Alzheimer's disease genes in Japanese. J Neurol Sci. 1998;160(1):76-81.
27. Jayadev S, Leverenz JB, Steinbart E, etal. Alzheimer's disease phenotypes and genotypes associated with mutations in presenilin 2. Brain. 2010;133(4):1143-1154.
28. To MD, Gokgoz N, Doyle TG, etal. Functional characterization of novel presenilin-2 variants identified in human breast cancers. Oncogene. 2008;25(25):3557-3564.
29. Ishikawa A, Piao YS, Miyashita A, etal. A mutant PSEN1 causes dementia with Lewy bodies and variant Alzheimer's disease. Ann Neurol. 2005;57(3):429-434.
30. Kumar-Singh S, Cras P, Wang R, etal. Dense-core senile plaques in the Flemish variant of Alzheimer's disease are vasocentric. Am J Pathol. 2002;161(2):507-520.
31. Kamino K, Orr HT, Payami H, etal. Linkage and mutational analysis of familial Alzheimer disease kindreds for the APP gene region. Am J Hum Genet. 1992;51(5):998-1014.
32. Giaccone G, Rossi G, Morbin M, Tagliavini F, Bugiani O. A713T mutation of the APP gene in an Italian family with Alzheimer disease and severe congophilic angiopathy. Neurobiol Aging. 2002;23(Suppl 1): S320.
33. Pasalar P, Najmabadi H, Noorian AR, etal. An Iranian family with Alzheimer's disease caused by a novel APP mutation (Thr714Ala). Neurology. 2002;58(10):1574-1575.
34. De Jonghe C, Kumar-Singh S, Cruts M, etal. Unusual Aβ amyloid deposition in Alzheimer's disease due to an APP T714I mutation at the γ42-secretase site. Neurobiol Aging. 2000;21(Suppl 1):S200.
35. Park HK, Na DL, Lee JH, Kim JW, Ki CS. Identification of PSEN1 and APP gene mutations in Korean patients with early-onset Alzheimer's disease. J Korean Med Sci. 2008;23(2):213-217.
36. Janssen JC, Beck JA, Campbell AT, etal. Early onset familial Alzheimer's disease: Mutation frequency in 31 families. Neurology. 2003;60(20):235-239.
37. Guerreiro RJ, Baquero M, Blesa R, etal. Genetic screening of Alzheimer's disease genes in Iberian and African samples yields novel mutations in presenilins and APP. Neurobiol Aging. 2008;31(5):725-731.
38. Yoshioka K, Miki T, Katsuya T, Ogihara T, Sakaki Y. The 717Val-Ile substitution in amyloid precursor protein is associated with familial Alzheimer's disease regardless of ethnic groups. Biochem Biophys Res Commun. 1991;178(3):1141-1146.
39. Goate A, Chartier-Harlin MC, Mullan M, etal. Segregation of a missense mutation in the amyloid precursor protein gene with familial Alzheimer's disease. Nature. 1991;349(6311):704-706.
40. Murrell JR, Hake AM, Quaid KA, Farlow MR, Ghetti B. Early-onset Alzheimer disease caused by a new mutation (V717L) in the amyloid precursor protein gene. Arch Neurol. 2000;57(6):885-887.
41. Thajeb P, Wang P, Chien CL, Harrigan R. Novel polymorphisms of the amyloid precursor protein (APP) gene in Chinese/Taiwanese patients with Alzheimer's disease. J Clin Neurosci. 2009;16(2):259-263.
42. Finckh U, Kuschel C, Anagnostouli M, etal. Novel mutations and repeated findings of mutations in familial Alzheimer disease. Neurogenetics. 2005;6(2):85-89.
43. Chartier-Harlin MC, Crawford F, Houlden H, etal. Early-onset Alzheimer's disease caused by mutations at codon 717 of the beta-amyloid precursor protein gene. Nature. 1991;353(6347):844-846.
44. Kwok JB, Li QX, Hallupp M, etal. Novel Leu723Pro amyloid precursor protein mutation increases amyloid beta42(43) peptide levels and induces apoptosis. Ann Neurol. 2000;47(2):249-253.
45. Theuns J, Marjaux E, Vandenbulcke M, etal. Alzheimer dementia caused by a novel mutation located in the APP C-terminal intracytosolic fragment. Hum Mutat. 2006;27(9):888-896.
46. Wakutani Y, Watanabe K, Adachi Y, etal. Novel amyloid precursor protein gene missense mutation (D678N) in probable familial Alzheimer's disease. J Neurol Neurosurg Psychiatry. 2004;75(7):1039-1042.
47. Brouwers N, Sleegers K, Van Broeckhoven C. Molecular genetics of Alzheimer's disease: an update. Ann Medicine. 2008;40(8):562-583.
48. Cruts M, van Duijn CM, Backhovens H, etal. Estimation of the genetic contribution of presenilin-1 and-2mutations in a population-based study of presenile Alzheimer disease. Hum Mol Genet. 1998;7(1):43-51.
49. Finckh U, Müller-Thomsen T, Mann U, etal. High prevalence of pathogenic mutations in patients with early-onset dementia detected by sequence analyses of four different genes. Am J Hum Genet. 2000;66(1):110-117.
50. Rogaeva EA, Fafel KC, Song YQ, etal. Screening for PS1mutations in a referral-based series of AD cases: 21 novel mutations. Neurology. 2001;57(4):621-625.
51. Campion D, Flaman JM, Brice A, etal. Mutations of the presenilin I gene in families with early-onset Alzheimer's disease. Hum Mol Genet. 1995;4(12):2373-2377.
52. Houlden H, Baker M, McGowan E, etal. Variant Alzheimer's disease with spastic paraparesis and cotton wool plaques is caused by PS-1 mutations that lead to exceptionally high amyloid-beta concentrations. Ann Neurol. 2000;48(5):806-808.
53. Ataka S, Tomiyama T, Takuma H, etal. A novel presenilin-1mutation (Leu85Pro) in early-onset Alzheimer disease with spastic paraparesis. Arch Neurol. 2004;61(11):1773-1776.
54. Queralt R, Ezquerra M, Lleó A, etal. A novel mutation (V89L) in the presenilin 1gene in a family with early onset Alzheimer's disease and marked behavioural disturbances. J Neurol Neurosurg Psychiatry. 2002;72(2):266-269.
55. Tedde A, Nacmias B, Ciantelli M, etal. Identification of new presenilin gene mutations in early-onset familial Alzheimer disease. Arch Neurol. 2003;60(11):1541-1544.
56. Arango D, Cruts M, Torres O, etal. Systematic genetic study of Alzheimer disease in Latin America: mutation frequencies of the amyloid beta precursor protein and presenilin genes in Colombia. Am J Med Genet. 2001;103(2):138-143.
57. Kamino K, Sato S, Sakaki Y, etal. Three different mutations of presenilin 1gene in early-onset Alzheimer's disease families. Neurosci Lett, 1997;208(3):195-198.
58. Fang B, Jia L, Jia J. Chinese Presenilin-1 V97L mutation enhanced Abeta42 levels in SH-SY5Y neuroblastoma cells. Neurosci Lett. 2006;406(1-2):33-37.
59. Raux G, Guyant-Maréchal L, Martin C, etal. Molecular diagnosis of autosomal dominant early onset Alzheimer's disease: an update. J Med Genet. 2005;42(10):793-795.
60. Gómez-Tortosa E, Barquero S, Barón M, etal. Clinical-genetic correlations in familial Alzheimer's disease caused by presenilin 1 mutations. J Alzheimers Dis. 2010;19(3):873-888.
61. Raux G, Gantier R, Thomas-Anterion C, etal. Dementia with prominent frontotemporal features associated with L113P presenilin 1 mutation. Neurology. 2000;55(10):1577-1579.
62. La Bella V, Liguori M, Cittadella R, etal. A novel mutation (Thr116Ile) in the presenilin 1gene in a patient with early-onset Alzheimer's disease. Eur J Neurol. 2004;11(8):521-524.
63. Anheim M, Hannequin D, Boulay C, Martin C, Campion D, Tranchant C. Ataxic variant of Alzheimer's disease caused by Pro117Ala PSEN1 mutation. J Neurol Neurosurg Psychiatry. 2007;78(12):1414-1415.
64. Dowjat WK, Kuchna I, Wisniewski T, Wegiel J. A novel highly pathogenic Alzheimer presenilin-1mutation in codon 117 (Pro117Ser): Comparison of clinical, neuropathological and cell culture phenotypes of Pro117Leu and Pro117Ser mutations. J Alzheimers Dis. 2004;6(1):31-43.
65. Zekanowski C, Styczyńska M, Pepłońska B, etal. Mutations in presenilin 1, presenilin 2 and amyloid precursor protein genes in patients with early-onset Alzheimer's disease in Poland. Exp Neurol. 2003;184(2):991-996.
66. Wisniewski T, Dowjat WK, Buxbaum JD, etal. A novel Polish presenilin-1mutation (P117L) is associated with familial Alzheimer's disease and leads to death as early as the age of 28 years. Neuroreport. 1998;9(2):217-221.
67. Hutton H, Busfield F, Wragg M, etal. Complete analysis of the presenilin 1gene in early onset Alzheimer's disease. Neuroreport. 1996;7(3):801-805.
68. Crook R, Ellis R, Shanks M, etal. Early-onset Alzheimer's disease with a presenilin-1mutation at the site corresponding to the Volga German presenilin-2 mutation. Ann Neurol. 1997;42(1):124-128.
69. Yasuda M, Maeda K, Hashimoto M, etal. A pedigree with a novel presenilin 1mutation at a residue that is not conserved in presenilin 2. Arch Neurol. 1999;56(1):65-69.
70. Dumanchin C, Brice A, Campion D, etal. De novo presenilin 1 mutations are rare in clinically sporadic, early onset Alzheimer's disease cases. French Alzheimer's Disease Study Group. J Med Genet. 1998;35(8):672-673.
71. Kim HJ, Kim HY, Ki CS, Kim SH. Presenilin 1gene mutation (M139I) in a patient with an early-onset Alzheimer's disease: clinical characteristics and genetic identification. Neurol Sci. 2010;31(8):781-783.
72. Palmer MS, Beck JA, Campbell TA, etal. Pathogenic presenilin 1mutations (P436S and I143F) in early-onset Alzheimer's disease in the UK. Hum Mutat. 1999;13(3):256.
73. Gallo M, Marcello N, Curcio SA, etal. A novel pathogenic PSEN1mutation in a family with Alzheimer's disease: phenotypical and neuropathological features. J Alzheimers Dis. 2011;25(3):425-431.
74. Hattori S, Sakuma K, Wakutani YS, etal. A novel presenilin 1mutation (Y154N) in a patient with early onset Alzheimer's disease with spastic paraparesis. Neurosci Lett. 2004;368(3):319-322.
75. Axelman K, Basun H, Lannfelt L. Wide range of disease onset in a family with Alzheimer disease and a His163Tyr mutation in the presenilin-1 gene. Arch Neurol. 1998;55(5):698-702.
76. Hong KS, Kim SP, Na DL, etal. Clinical and genetic analysis of a pedigree of a thirty-six-year-old familial Alzheimer's disease patient. Biol Psychiatry. 1997;42(12):1172-1176.
77. Kim J, Bagyinszky E, Chang YH, etal. A novel PSEN1 H163P mutation in a patient with early-onset Alzheimer's disease: clinical, neuroimaging, and neuropathological findings. Neurosci Lett. 2012;530(2):109-114.
78. Higuchi S, Yoshino A, Matsui T, etal. A novel PS1 Mutation (W165G) in a Japanese family with early-onset Alzheimer's disease. Alzheimer Reports. 2000;3(4):227-231.
79. Knight WD, Kennedy J, Mead S, etal. A novel presenilin 1 deletion (p. L166del) associated with early onset familial Alzheimer's disease. Eur J Neurol. 2007;14(7):829-831.
80. Pantieri R, Pardini M, Cecconi M, etal. A novel presenilin 1L166H mutation in a pseudo-sporadic case of early-onset Alzheimer's disease. Neurol Sci. 2005;26(5):349-350.
81. Moehlmann T, Winkler E, Xia X, etal. Presenilin-1mutations of leucine 166 equally affect the generation of the Notch and APP intracellular domains independent of their effect on Abeta 42 production. Proc Natl Acad Sci U S A. 2002;99(12):8025-8030.
82. Lleó A, Blesa R, Queralt R, etal. Frequency of mutations in the presenilin and amyloid precursor protein genes in early-onset Alzheimer disease in Spain. Arch Neurol. 2002;59(11):1759-1763.
83. Takao M, Ghetti B, Murrell JR, etal. Ectopic white matter neurons, a developmental abnormality that may be caused by the PSEN1 S169L mutation in a case of familial AD with myoclonus and seizures. J Neuropathol Exp Neurol. 2001;60(12):1137-1152.
84. Guo J, Wei J, Liao S, Wang L, Jiang H, Tang B. A novel presenilin 1mutation (Ser169del) in a Chinese family with early-onset Alzheimer's disease. Neurosci Lett. 2010;468(1):34-37.
85. Piccini A, Zanusso G, Borghi R, etal. Association of a presenilin 1 S170F mutation with a novel Alzheimer disease molecular phenotype. Arch Neurol. 2007;64(5):738-745.
86. Kasuga K, Ohno T, Ishihara T, etal. Depression and psychiatric symptoms preceding onset of dementia in a family with early-onset Alzheimer disease with a novel PSEN1 mutation. J Neurol. 2009;256(8):1351-1353.
87. Klünemann HH, Rogaeva E, Neumann M, etal. Novel PS1mutation in a Bavarian kindred with familial Alzheimer disease. Alzheimer Dis Assoc Disord. 2004;18(4):256-258.
88. Dermaut B, Kumar-Singh S, Engelborghs S, etal. A novel presenilin 1 mutation associated with Pick's disease but not beta-amyloid plaques. Ann Neurol. 2004;55(5):617-626.
89. Yasuda M, Maeda K, Ikejiri Y, Kawamata T, Kuroda S, Tanaka C. A novel missense mutation in the presenilin-1gene in a familial Alzheimer's disease pedigree with abundant amyloid angiopathy. Neurosci Lett. 1997;232(1):29-32.
90. Goldman JS, Reed B, Gearhart R, Kramer JH, Miller BL. Very early-onset familial Alzheimer's disease: a novel presenilin 1 mutation. Int J Geriatr Psychiatry. 2002;17(7):649-651.
91. Sugiyama N, Suzuki K, Matsumura T, etal. A novel missense mutation (G209R) in exon 8 of the presenilin 1gene in a Japanese family with presenile familial Alzheimer's disease. Hum Mutat. 1999;14(1):90.
92. Poorkaj P, Sharma V, Anderson L, etal. Missense mutations in the chromosome 14 familial Alzheimer's disease presenilin 1 gene. Hum Mutat. 1998;11(3):216-222.
93. Ringman JM, Gylys KH, Medina LD, etal. Biochemical, neuropathological, and neuroimaging characteristics of early-onset Alzheimer's disease due to a novel PSEN1 mutation. Neurosci Lett. 2011;487(3):287-292.
94. Norton JB, Cairns NJ, Chakraverty S, etal. Presenilin1 G217R mutation linked to Alzheimer disease with cotton wool plaques. Neurology. 2009;73(6):480-482.
95. Takao M, Ghetti B, Hayakawa I, etal. A novel mutation (G217D) in the Presenilin 1gene (PSEN1) in a Japanese family: presenile dementia and parkinsonism are associated with cotton wool plaques in the cortex and striatum. Acta Neuropathol. 2002;104(2):155-170.
96. Smith MJ, Gardner RJ, Knight MA, etal. Early-onset Alzheimer's disease caused by a novel mutation at codon 219 of the presenilin-1 gene. Neuroreport. 1999;10(3):503-507.
97. Miklossy J, Taddei K, Suva D, etal. Two novel presenilin-1mutations (Y256S and Q222H) are associated with early-onset Alzheimer's disease. Neurobiol Aging. 2003;24(5):655-662.
98. Uttner I, Kirchheiner J, Tumani H, etal. A novel presenilin1mutation (Q223R) associated with early onset Alzheimer's disease, dysarthria and spastic paraparesis and decreased Abeta levels in CSF. Eur J Neurol. 2010;17(4):631-633.
99. Zekanowski C, Golan MP, Krzyśko KA, etal. Two novel presenilin 1 gene mutations connected with frontotemporal dementia-like clinical phenotype: genetic and bioinformatic assessment. Exp Neurol. 2006;200(1):82-88.
100. Coleman P, Kurlan R, Crook R, Werner J, Hardy J. A new presenilin Alzheimer's disease case confirms the helical alignment of pathogenic mutations in transmembrane domain 5. Neurosci Lett. 2004;364(3):139-140.
101. Houlden H, Crook R, Dolan RJ, McLaughlin J, Revesz T, Hardy J. A novel presenilin mutation (M233V) causing very early onset Alzheimer's disease with Lewy bodies. Neurosci Lett. 2001;313(1-2):93-95.
102. Aldudo J, Bullido MJ, Valdivieso F. DGGE method for the mutational analysis of the coding and proximal promoter regions of the Alzheimer's disease presenilin-1gene: two novel mutations. Hum Mutat. 1991;14(5):433-439.
103. Portet F, Dauvilliers Y, Campion D, etal. Very early onset AD with a de novo mutation in the presenilin 1gene (Met 233Leu). Neurology. 2003;61(8):1136-1137.
104. Sodeyama N, Iwata T, Ishikawa K, etal. Very early onset Alzheimer's disease with spastic paraparesis associated with a novel presenilin 1mutation (Phe237Ile). J Neurol Neurosurg Psychiatry. 2001;71(4):556-557.
105. Lladó A, Fortea J, Ojea T, etal. A novel PSEN1mutation (K239N) associated with Alzheimer's disease with wide range age of onset and slow progression. Eur J Neurol. 2010;17(7):994-996.
106. Edwards-Lee T, Wen J, Bell J, Hardy J, Chung J, Momeni P. A presenilin-1mutation (T245P) in transmembrane domain 6 causes early onset Alzheimer's disease. Neurosci Lett. 2006;398(3): 251-252.
107. Kowalska A, Wender M, Florczak J, etal. Molecular genetics of Alzheimer's disease: presenilin 1gene analysis in a cohort of patients from the Poznań region. J Appl Genet. 2003;44(2):231-234.
108. Furuya H, Yasuda M, Terasawa K, etal. A novel mutation (L250V) in the presenilin 1gene in a Japanese familial Alzheimer's disease with myoclonus and generalized convulsion. J Neurol Sci. 2003;209(1-2):75-77.
109. Tabira T, Chui DH, Nakayama H, Kuroda S, Shibuya M. Alzheimer's disease with spastic paresis and cotton wool type plaques. J Neurosci Res. 2002;70(3):367-372.
110. Verkkoniemi A, Somer M, Rinne OJ, etal. Variant Alzheimer's disease with spastic paraparesis: clinical characterization. Neurology. 2000;54(5):1103-1109.
111. Dumanchin C, Tournier I, Martin C, etal. Biological effects of four PSEN1 gene mutations causing Alzheimer disease with spastic paraparesis and cotton wool plaques. Hum Mutat. 2006;27(10):1063.
112. Ikeda M, Sharma V, Sumi SM, etal. The clinical phenotype of two missense mutations in the presenilin I gene in Japanese patients. Ann Neurol. 1996;40(6):912-917.
113. Jiménez Caballero PE, Lladó A, de Diego Boguna C, Martin Correa E, Serviá Candela M, Marsal Alonso C. A novel presenilin 1 mutation (V261L) associated with presenile Alzheimer's disease and spastic paraparesis. Eur J Neurol. 2008;15(9):991-994.
114. Forsell C, Froelich S, Axelman K, etal. A novel pathogenic mutation (Leu262Phe) found in the presenilin 1gene in early-onset Alzheimer's disease. Neurosci Lett. 1997;234(1):3-6.
115. Wasco W, Pettingell WP, Jondro PD, etal. Familial Alzheimer's chromosome 14 mutations. Nat Med. 1995;1(9):848.
116. Akatsu H, Yamagata H, Wake A, etal. The first autopsy case report of familial Alzheimer's disease (AD) associated with a mutation at G266S in the presenilin 1 (PSEN1) gene. Alzheimers Dement. 2008; 4 Suppl 2:T578.
117. Matsubara-Tsutsui M, Yasuda M, Yamagata H, etal. Molecular evidence of presenilin 1mutation in familial early onset dementia. Am J Med Genet. 2002;114(3):292-298.
118. Perez-Tur J, Croxton R, Wright K, etal. A further presenilin 1 mutation in the exon 8 cluster in familial Alzheimer's disease. Neurodegeneration. 1996;5(3):207-212.
119. Kwok JB, Halliday GM, Brooks WS, etal. Presenilin-1mutation L271V results in altered exon 8splicing and Alzheimer's disease with non-cored plaques and no neuritic dystrophy. J Biol Chem. 2003;278(9):6748-6754.
120. Kwok JB, Taddei K, Hallupp M, etal. Two novel (M233T and R278T) presenilin-1mutations in early-onset Alzheimer's disease pedigrees and preliminary evidence for association of presenilin-1mutations with a novel phenotype. Neuroreport. 1997;8(6): 1537-1542.
121. Raman A, Lin X, Suri M, Hewitt M, Constantinescu CS, Phillips MF. A presenilin 1mutation (Arg278Ser) associated with early onset Alzheimer's disease and spastic paraparesis. J Neurol Sci. 2007;260(1-2):78-82.
122. Assini A, Terreni L, Borghi R, etal. Pure spastic paraparesis associated with a novel presenilin 1 R278K mutation. Neurology. 2003;60(1):150.
123. Godbolt AK, Beck JA, Collinge J, etal. A presenilin 1 R278I mutation presenting with language impairment. Neurology. 2004;63(9):1702-1704.
124. Dermaut B, Kumar-Singh S, De Jonghe C, etal. Cerebral amyloid angiopathy is a pathogenic lesion in Alzheimer's disease due to a novel presenilin 1 mutation. Brain. 2001;124(12):2383-2392.
125. Hamaguchi T, Morinaga A, Tsukie T, Kuwano R, Yamada M. A novel presenilin 1mutation (L282F) in familial Alzheimer's disease. J Neurol. 2009;256(9):1575-1577.
126. Aoki M, Abe K, Oda N, etal. A presenilin-1mutation in a Japanese family with Alzheimer's disease and distinctive abnormalities on cranial MRI. Neurology. 1997;48(4):1118-1120.
127. Ikeuchi T, Kaneko H, Miyashita A, etal. Mutational analysis in early-onset familial dementia in the Japanese population. The role of PSEN1 and MAPT R406W mutations. Dement Geriatr Cogn Disord. 2008;26(1):43-49.
128. Sánchez-Valle R, Lladó A, Ezquerra M, Rey MJ, Rami L, Molinuevo JL. A novel mutation in the PSEN1gene (L286P) associated with familial early-onset dementia of Alzheimer type and lobar haematomas. Eur J Neurol. 2007;14(12):1409-1412.
129. Dintchov Traykov L, Mehrabian S, Van den Broeck M, etal. Novel PSEN1mutation in a Bulgarian patient with very early-onset Alzheimer's disease, spastic paraparesis, and extrapyramidal signs. Am J Alzheimers Dis Other Demen. 2009;24(5):404-407.
130. Cruts M, Backhovens H, Wang SY, etal. Molecular genetic analysis of familial early-onset Alzheimer's disease linked to chromosome 14q24.3. Hum Mol Genet. 1995;4(12):2363-2371.
131. Yasuda M, Maeda S, Kawamata T, etal. Novel presenilin-1mutation with widespread cortical amyloid deposition but limited cerebral amyloid angiopathy. J Neurol Neurosurg Psychiatry. 2000;68(2):220-223.
132. Shrimpton AE, Schelper RL, Linke RP, etal. A presenilin 1mutation (L420R) in a family with early onset Alzheimer disease, seizures and cotton wool plaques, but not spastic paraparesis. Neuropathology. 2007;27(3):228-232.
133. Robles A, Sobrido MJ, García-Murias M, etal. Clinical picture of a patient with a novel PSEN1mutation (L424V). Am J Alzheimers Dis Other Demen. 2009;24(1):40-45.
134. Matsushita S, Arai H, Okamura N, etal. Clinical and biomarker investigation of a patient with a novel presenilin-1mutation (A431V) in the mild cognitive impairment stage of Alzheimer's disease. Biol Psychiatry. 2002;52(9):907-910.
135. Beck JA, Poulter M, Campbell TA, etal. Somatic and germline mosaicism in sporadic early-onset Alzheimer's disease. Hum Mol Genet. 2004;13(12):1219-1224.
136. Piscopo P, Marcon G, Piras MR, etal. A novel PSEN2mutation associated with a peculiar phenotype. Neurology. 2008;70(17):1549-1554.
137. Lao JI, Beyer K, Fernández-Novoa L, Cacabelos R. A novel mutation in the predicted TM2 domain of the presenilin 2gene in a Spanish patient with late-onset Alzheimer's disease. Neurogenetics. 1998;1(4):293-296.
138. Piscopo P, Talarico G, Crestini A, etal. A novel mutation in the predicted TMIII domain of the PSEN2gene in an Italian pedigree with atypical Alzheimer's disease. J Alzheimers Dis. 2010;20(1):43-47.
139. Finckh U, Alberici A, Antoniazzi M, etal. Variable expression of familial Alzheimer disease associated with presenilin 2mutation M239I. Neurology. 2000;54(10):2006-2008.
140. Lleó A, Blesa R, Gendre J, etal. A novel presenilin 2gene mutation (D439A) in a patient with early-onset Alzheimer's disease. Neurology. 2001;57(10):1926-1928.
141. Bu G. Apolipoprotein E and its receptors in Alzheimer's disease: pathways, pathogenesis and therapy. Nat Rev Neurosci. 2009;10(5):333-344.
142. Green RC, Roberts JS, Cupples LA, etal; REVEAL Study Group. Disclosure of APOE genotype for risk of Alzheimer's disease. N Engl J Med. 2009;361(3):245-254.
143. Rihn BH, Berrahmoune S, Jouma M, Chamaa S, Marcocci L, Le Faou A. APOE genotyping: comparison of three methods. Clin Exp Med. 2009;9(1):61-65.
144. Mahley RW, Huang Y. Alzheimer disease: multiple causes, multiple effects of apolipoprotein E4, and multiple therapeutic approaches. Ann Neurol. 2009;65(6):623-625.
145. Mahley RW, Huang Y. Apolipoprotein (apo) E4 and Alzheimer's disease: unique conformational and biophysical properties of apoE4 can modulate neuropathology. Acta Neurol Scand Suppl. 2006;185:8-14.
146. Mahley RW, Weisgraber KH, Huang Y. Apolipoprotein E4: a causative factor and therapeutic target in neuropathology, including Alzheimer's disease. Proc Natl Acad Sci U S A. 2006;103(15):5644-5651.
147. Mahley RW, Rall SC Jr. Apolipoprotein E: far more than a lipid transport protein. Annu Rev Genomics Hum Genet. 2000;1:507-537.
148. Liu CC, Kanekiyo T, Xu H, Bu G. Apolipoprotein E and Alzheimer disease: risk, mechanisms and therapy. Nat Rev Neurol. 2013;9(2): 106-118.
149. Kim KW, Jhoo JH, Lee KU, etal. Association between apolipoprotein E polymorphism and Alzheimer's disease in Koreans. Neurosci Lett. 1999;277(3):145-148.
150. Coon KD, Myers AJ, Craig DW, etal. A high-density whole-genome association study reveals that APOE is the major susceptibility gene for sporadic late-onset Alzheimer's disease. J Clin Psychiatry. 2007;68(4): 613-618.
151. Waring SC, Rosenberg RN. Genome-wide association studies in Alzheimer disease. Arch Neurol. 2008;65(3):329-334.
152. Bertram L, McQueen MB, Mullin K, Blacker D, Tanzi RE. Systematic meta-analyses of Alzheimer disease genetic association studies: the AlzGene database. Nat Genet. 2007;39(1):17-23.
153. Bettens K, Sleegers K, Van Broeckhoven C. Genetic insights in Alzheimer's disease. Lancet Neurol. 2013;12(1):92-104.
154. Calero M, Rostagno A, Matsubara E, Zlokovic B, Frangione B, Ghiso J. Apolipoprotein J (clusterin) and Alzheimer's disease. Microsc Res Tech. 2000;50(4):305-315.
155. Lambert JC, Heath S, Even G, etal; European Alzheimer's Disease Initiative Investigators, de Pancorbo MM, Lendon C, etal. Genome-wide association study identifies variants at CLU and CR1 associated with Alzheimer's disease. Nat Genet. 2009;41(10):1094-1099.
156. Crehan H, Holton P, Wray S, Pocock J, Guerreiro R, Hardy J. Complement receptor 1 (CR1) and Alzheimer's disease. Immunobiology. 2012;217(2):244-250.
157. Xiao Q, Gil SC, Yan P, etal. Role of phosphatidylinositol clathrin assembly lymphoid-myeloid leukemia (PICALM) in intracellular amyloid precursor protein (APP) processing and amyloid plaque pathogenesis. J Biol Chem. 2012;287(25):21279-21289.
158. Harold D, Abraham R, Hollingworth P, etal. Genome-wide association study identifies variants at CLU and PICALM associated with Alzheimer's disease. Nat Genet. 2009;41(10):1088-1093.
159. Rogaeva E, Meng Y, Lee JH, etal. The neuronal sortilin-related receptor SORL1 is genetically associated with Alzheimer disease. Nat Genet. 2007;39(2):168-177.
160. Meng Y, Lee JH, Cheng R, St George-Hyslop P, Mayeux R, Farrer LA. Association between SORL1 and Alzheimer's disease in a genome-wide study. Neuroreport. 2007;18(17):1761-1764.
161. Cruchaga C, Nowotny P, Kauwe JS, etal; Alzheimer's Disease Neuroimaging Initiative. Association and expression analyses with single-nucleotide polymorphisms in TOMM40in Alzheimer disease. Arch Neurol. 2011;68(8):1013-1019.
162. Hu X, Pickering E, Liu YC, etal; Alzheimer's Disease Neuroimaging Initiative. Meta-analysis for genome-wide association study identifies multiple variants at the BIN1 locus associated with late-onset Alzheimer's disease. PLoS One. 2011;6(2):e16616.
163. De Ferrari GV, Papassotiropoulos A, Biechele T, etal. Common genetic variation within the low-density lipoprotein receptor-related protein 6 and late-onset Alzheimer's disease. Proc Natl Acad Sci U S A. 2007;104(22):9434-9439.
164. Miyashita A, Arai H, Asada TA, etal. Japanese Genetic Study Consortium for Alzeheimer's Disease. Genetic association of CTNNA3 with late-onset Alzheimer's disease in females. Hum Mol Genet. 2007;16(23):2854-2869.
165. Ertekin-Taner N, Ronald J, Asahara H, etal. Fine mapping of the alpha-T catenin gene to a quantitative trait locus on chromosome 10 in late-onset Alzheimer's disease pedigrees. Hum Mol Genet. 2003;12(23):3133-3143.
166. Reiman EM, Webster JA, Myers AJ, etal. GAB2 alleles modify Alzheimer's risk in APOE epsilon4 carriers. Neuron. 2007;54(5):713-720.
167. Pan XL, Ren RJ, Wang G, Tang HD, Chen SD. The Gab2in signal transduction and its potential role in the pathogenesis of Alzheimer's disease. Neurosci Bull. 2010;26(3):241-246.
168. Liang WS, Chen K, Lee W, etal. Association between GAB2 haplotype and higher glucose metabolism in Alzheimer's disease-affected brain regions in cognitively normal APOEε4 carriers. Neuroimage. 2011;54(3):1896-1902.
169. Bettens K, Brouwers N, Engelborghs S, etal. DNMBP is genetically associated with Alzheimer dementia in the Belgian population. Neurobiol Aging. 2009;30(12):2000-2009.
170. Kim M, Suh J, Romano D, etal. Potential late-onset Alzheimer's disease-associated mutations in the ADAM10gene attenuate {alpha}-secretase activity. Hum Mol Genet. 2009;18(20):3987-3996.
171. Holton P, Ryten M, Nalls M, etal. Initial assessment of the pathogenic mechanisms of the recently identified Alzheimer risk Loci. Ann Hum Genet. 2013;77(2):85-105.
172. Tanaka N, Abe-Dohmae S, Iwamoto N, Yokoyama S. Roles of ATP-binding cassette transporter A7in cholesterol homeostasis and host defense system. J Atheroscler Thromb. 2011;18(4):274-281.
173. Reitz C, Jun G, Naj A, Rajbhandary R, etal; Alzheimer Disease Genetics Consortium. Variants in the ATP-binding cassette transporter (ABCA7), apolipoprotein E ∈4, and the risk of late-onset Alzheimer disease in African Americans. JAMA. 2013;309(14):1483-1492.
174. Klesney-Tait J, Turnbull IR, Colonna M. The TREM receptor family and signal integration. Nat Immunol. 2006;7(12):1266-1273.
175. Jonsson T, Stefansson H, Steinberg S, etal. Variant of TREM2 associated with the risk of Alzheimer's disease. N Engl J Med. 2013;368(2):107-116.
176. Guerreiro R, Wojtas A, Bras J, etal; Alzheimer Genetic Analysis Group. TREM2 variants in Alzheimer's disease. N Engl J Med. 2013;368(2):117-127.
177. Bradshaw EM, Chibnik LB, Keenan BT, etal; Alzheimer Disease Neuroimaging Initiative, Morris MC, Evans DA, etal. CD33Alzheimer's disease locus: altered monocyte function and amyloid biology. Nat Neurosci. 2013;16(7):848-850.
178. NSW Government Centre for Genetics Testing. DNA Genetic Testing: Screening for Genetic Conditions and Genetic Susceptibility. Fact Sheet 21. Sydney: NSW Government Centre for Genetics Testing; nd. Available from: http://www.genetics.edu.au/Information/Genetics-Fact-Sheets/DNAGeneticTestingTestingforGeneticConditionsandGeneticSusceptibilityFS21. Accessed September 30, 2013.
179. Reznik-Wolf H, Treves TA, Shabtai H, etal. Germline mutational analysis of presenilin 1 and APP genes in Jewish-Israeli individuals with familial or early-onset Alzheimer disease using denaturing gradient gel electrophoresis (DGGE). Eur J Hum Genet. 1998;6(2):176-180.
180. Reznik-Wolf H, Treves TA, Davidson MA, etal. A novel mutation of presenilin 1in familial Alzheimer's disease in Israel detected by denaturing gradient gel electrophoresis. Hum Genet. 1996;98(6):700-702.
181. Orita M, Iwahana H, Kanazawa H, Hayashi K, Sekiya T. Detection of polymorphisms of human DNA by gel electrophoresis as single-strand conformation polymorphisms. Proc Natl Acad Sci U S A. 1989;86(8):2766-2770.
182. Hayashi K. PCR-SSCP: a simple and sensitive method for detection of mutations in the genomic DNA. PCR Methods Appl. 1991;1(1):34-38.
183. Qiu P, Shandilya H, D'Alessio JM, O'Connor K, Durocher J, Gerard GF. Mutation detection using Surveyor nuclease. Biotechniques. 2004;36(4):702-707.
184. Bannwarth S, Procaccio V, Paquis-Flucklinger V. Surveyor Nuclease: a new strategy for a rapid identification of heteroplasmic mitochondrial DNA mutations in patients with respiratory chain defects. Hum Mutat. 2005;25(6):575-582.
185. Mitani N, Tanaka S, Okamoto Y. Surveyor nuclease-based genotyping of SNPs. Clin Lab. 2006;52(7-8):385-386.
186. Yang YG, Kim JY, Park SJ, Kim SW, Jeon OH, Kim DS. Apolipoprotein E genotyping by multiplex tetra-primer amplification refractory mutation system PCR in single reaction tube. J Biotechnol. 2007;131(2):106-110.
187. Nauck M, Hoffmann MM, Wieland H, März W. Evaluation of the apo E genotyping kit on the LightCycler. Clin Chem. 2000;46(5):722-724.
188. Wu YY, Delgado R, Costello R, Sunderland T, Dukoff R, Csako G. Quantitative assessment of apolipoprotein E genotypes by image analysis of PCR-RFLP fragments. Clin Chim Acta. 2000;293(1-2):213-221.
189. Tanzi RE. The genetics of Alzheimer disease. Cold Spring Harb Perspect Med. 2012;2:a006296.
190. Lin B, Wang J, Cheng Y. Recent Patents and Advances in the Next-Generation Sequencing Technologies. Recent Pat Biomed Eng. 2008;2008(1):60-67.
191. Morozova O, Marra MA. Applications of next-generation sequencing technologies in functional genomics. Genomics. 2008;92(5):255-264.
192. Jin SC, Pastor P, Cooper B, etal; Ibero-American Alzheimer Disease Genetics Group Researchers, Cruchaga C. Pooled-DNA sequencing identifies novel causative variants in PSEN1, GRN and MAPT in a clinical early-onset and familial Alzheimer's disease Ibero-American cohort. Alzheimers Res Ther. 2012;4(4):34.
193. Vallania FL, Druley TE, Ramos E, etal. High-throughput discovery of rare insertions and deletions in large cohorts. Genome Res. 2010;20(12):1711-1718.
194. Twine NA, Janitz K, Wilkins MR, Janitz M. Whole transcriptome sequencing reveals gene expression and splicing differences in brain regions affected by Alzheimer's disease. PLoS One. 2011;6(1):e16266.
195. Sutherland GT, Janitz M, Kril JJ. Understanding the pathogenesis of Alzheimer's disease: will RNA-Seq realize the promise of transcriptomics? J Neurochem. 2011;116(6):937-946.
196. Neumann PJ, Hammitt JK, Mueller C, etal. Public attitudes about genetic testing for Alzheimer's disease. Health Aff (Millwood). 2001;20(5):252-264.
197. Aisen PS, Vellas B, Hampel H. Moving towards early clinical trials for amyloid-targeted therapy in Alzheimer's disease. Nat Rev Drug Discov. 2013;12(4):324.
198. Marguerat S, Wilhelm BT, Bähler J. Next-generation sequencing: applications beyond genomes. Biochem Soc Trans. 2008;36(Pt 5): 1091-1096.
199. Lill CM, Bertram L. Towards unveiling the genetics of neurodegenerative diseases. Semin Neurol. 2011;31(5):531-541.