Use of genetic variation as biomarkers for mild cognitive impairment and progression of mild cognitive impairment to dementia

Journal of Alzheimer's Disease

Volumn 19, Issue 1, 2010, Pages 229-251

  Reitz, Christiane ^a,b   Mayeux, Richard ^a,b,c  

^a Columbia University ^*  (United States)

^b Taub Institute for Research on Alzheimer's Disease and the Aging Brain and the Gertrude H Sergievsky Center   (United States)

^c NONE   (United States)

Author keywords

Alzheimer's disease; APOE; Cognition; Genes; Mild cognitive impairment; SORL1

Indexed keywords

ALPHA 2 MACROGLOBULIN; APOLIPOPROTEIN E; CATENIN; CHOLINESTERASE; GLUTATHIONE TRANSFERASE; GLYCERALDEHYDE 3 PHOSPHATE DEHYDROGENASE; INSULINASE; NICOTINIC RECEPTOR BETA2; SORTILIN; TOLL LIKE RECEPTOR 4;

AGED; CALCIUM HOMEOSTASIS; CHROMOSOME 10Q; CHROMOSOME 12P; CHROMOSOME 19Q; CHROMOSOME 6P; CHROMOSOME 9Q; COGNITION; COGNITIVE DEFECT; DEMENTIA; DISEASE COURSE; GENE MAPPING; GENETIC RISK; GENETIC VARIABILITY; HUMAN; PHENOTYPE; PRIORITY JOURNAL; REVIEW; SCREENING; SENSITIVITY AND SPECIFICITY;

EID: 75149145165     PISSN: 13872877     EISSN: None     Source Type: Journal    
DOI: 10.3233/JAD-2010-1255     Document Type: Review

References (157)

1. Ferri CP, Prince M, Brayne C, Brodaty H, Fratiglioni L, Ganguli M, Hall K, Hasegawa K, Hendrie H, Huang Y, Jorm A, Mathers C, Menezes PR, Rimmer E, Scazufca M (2005) Global prevalence of dementia: a Delphi consensus study. Lancet 366, 2112-2117.
2. Fratiglioni L, De Ronchi D, Aguero-Torres H (1999) Worldwide prevalence and incidence of dementia. Drugs Aging 15, 365-375.
3. Brookmeyer R, Gray S, Kawas C (1998) Projections of Alzheimer's disease in the United States and the public health impact of delaying disease onset. Am J Public Health 88, 1337-1342.
4. McKhann G, Drachman D, Folstein M, Katzman R, Price D, Stadlan EM (1984) Clinical diagnosis of Alzheimer's disease: report of the NINCDS-ADRDAWork Group under the auspices of Department of Health and Human Services Task Force on Alzheimer's Disease. Neurology 34, 939-944.
5. Lopez OL, Swihart AA, Becker JT, Reinmuth OM, Reynolds CF, 3rd, Rezek DL, Daly FL, 3rd (1990) Reliability of NINCDS-ADRDA clinical criteria for the diagnosis of Alzheimer's disease. Neurology 40, 1517-1522.
6. Kukull WA, Larson EB, Reifler BV, Lampe TH, Yerby M, Hughes J (1990) Interrater reliability of Alzheimer's disease diagnosis. Neurology 40, 257-260.
7. Schofield PW, Tang M, Marder K, Bell K, Dooneief G, Lantigua R, Wilder D, Gurland B, Stern Y, Mayeux R (1995) Consistency of clinical diagnosis in a community-based longitudinal study of dementia and Alzheimer's disease. Neurology 45, 2159-2164.
8. Morris JC, McKeel DW, Jr., Fulling K, Torack RM, Berg L (1988) Validation of clinical diagnostic criteria for Alzheimer's disease. Ann Neurol 24, 17-22.
9. Burns A, Luthert P, Levy R, Jacoby R, Lantos P (1990) Accuracy of clinical diagnosis of Alzheimer's disease. BMJ 301, 1026.
10. Petersen RC (2004) Mild cognitive impairment as a diagnostic entity. J Intern Med 256, 183-194.
11. Petersen RC, Smith GE,Waring SC, Ivnik RJ, Tangalos EG, Kokmen E (1999) Mild cognitive impairment: clinical characterization and outcome. Arch Neurol 56, 303-308. (Pubitemid 29120227)
12. Petersen RC, Stevens JC, Ganguli M, Tangalos EG, Cummings JL, DeKosky ST (2001) Practice parameter: early detection of dementia: mild cognitive impairment (an evidencebased review). Report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology 56, 1133-1142.
13. Petersen RC, Doody R, Kurz A, Mohs RC, Morris JC, Rabins PV, Ritchie K, Rossor M, Thal L, Winblad B (2001) Current concepts in mild cognitive impairment. Arch Neurol 58, 1985-1992.
14. Larrieu S, Letenneur L, Orgogozo JM, Fabrigoule C, Amieva H, Le Carret N, Barberger-Gateau P, Dartigues JF (2002) Incidence and outcome of mild cognitive impairment in a population-based prospective cohort. Neurology 59, 1594-1599.
15. Palmer K, Wang HX, Backman L, Winblad B, Fratiglioni L (2002) Differential evolution of cognitive impairment in nondemented older persons: results from the Kungsholmen Project. Am J Psychiatry 159, 436-442.
16. Meyer JM, Breitner JC (1998) Multiple threshold model for the onset of Alzheimer's disease in the NAS-NRC twin panel. Am J Med Genet 81, 92-97.
17. Breitner JC, Wyse BW, Anthony JC, Welsh-Bohmer KA, Steffens DC, Norton MC, Tschanz JT, Plassman BL, Meyer MR, Skoog I, Khachaturian A (1999) APOE-epsilon4 count predicts age when prevalence of AD increases, then declines: the Cache County Study. Neurology 53, 321-331.
18. Corder EH, Saunders AM, Strittmatter WJ, Schmechel DE, Gaskell PC, SmallGW, Roses AD, Haines JL, Pericak-Vance MA (1993) Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer's disease in late onset families. Science 261, 921-923.
19. Gomez-Isla T,West HL, Rebeck GW, Harr SD, Growdon JH, Locascio JJ, Perls TT, Lipsitz LA, Hyman BT (1996) Clinical and pathological correlates of apolipoprotein E epsilon 4 in Alzheimer's disease. Ann Neurol 39, 62-70.
20. Holmes C, Levy R, McLoughlin DM, Powell JF, Lovestone S (1996) Apolipoprotein E: non-cognitive symptoms and cognitive decline in late onset Alzheimer's disease. J Neurol Neurosurg Psychiatry 61, 580-583.
21. Hyman BT, Gomez-Isla T, Rebeck GW, Briggs M, Chung H, West HL, Greenberg S, Mui S, Nichols S,Wallace R, Growdon JH (1996) Epidemiological, clinical, and neuropathological study of apolipoprotein E genotype in Alzheimer's disease. Ann N Y Acad Sci 802, 1-5. (Pubitemid 27055493)
22. Kurz A, Altland K, Lautenschlager N, Zimmer R, Busch R, Gerundt I, Lauter H, Muller U (1996) Apolipoprotein E type 4 allele and Alzheimer's disease: effect on age at onset and relative risk in different age groups. J Neurol 243, 452-456.
23. Murman DL, Foster NL, Kilgore SP, McDonagh CA, Fink JK (1996) Apolipoprotein E and Alzheimer's disease: strength of association is related to age at onset. Dementia 7, 251-255.
24. Poirier J, Davignon J, Bouthillier D, Kogan S, Bertrand P, Gauthier S (1993) Apolipoprotein E polymorphism and Alzheimer's disease. Lancet 342, 697-699.
25. Roses AD (1997) Alzheimer's disease: the genetics of risk. Hosp Pract (Minneap) 32, 51-55, 58-63, 67-159
26. Tang MX, Maestre G, TsaiWY, Liu XH, Feng L, Chung WY, Chun M, Schofield P, Stern Y, Tycko B, Mayeux R (1996) Relative risk of Alzheimer disease and age-at-onset distributions, based on APOE genotypes among elderly African Americans, Caucasians, and Hispanics in New York City. Am J Hum Genet 58, 574-584.
27. Barabash A, Marcos A, Ancin I, Vazquez-Alvarez B, de Ugarte C, Gil P, Fernandez C, Encinas M, Lopez-Ibor JJ, Cabranes JA (2009) APOE, ACT and CHRNA7 genes in the conversion from amnestic mild cognitive impairment to Alzheimer's disease. Neurobiol Aging 30, 1254-1264.
28. Petersen RC, Smith GE, Ivnik RJ, Tangalos EG, Schaid DJ, Thibodeau SN, Kokmen E, Waring SC, Kurland LT (1995) Apolipoprotein E status as a predictor of the development of Alzheimer's disease in memory-impaired individuals. JAMA 273, 1274-1278.
29. Sasaki M, Kodama C, Hidaka S, Yamashita F, Kinoshita T, Nemoto K, Ikejima C, AsadaT(2009) Prevalence of four subtypes of mild cognitive impairment and APOE in a Japanese community. Int J Geriatr Psychiatry bf 24, 1119-1126.
30. Tyas SL, Salazar JC, Snowdon DA, Desrosiers MF, Riley KP, Mendiondo MS, Kryscio RJ (2007) Transitions to mild cognitive impairments, dementia, and death: findings from the Nun Study. Am J Epidemiol 165, 1231-1238.
31. Blom ES, Giedraitis V, Zetterberg H, Fukumoto H, Blennow K, Hyman BT, Irizarry MC,Wahlund LO, Lannfelt L, IngelssonM( 2009) Rapid progression from mild cognitive impairment to Alzheimer's disease in subjects with elevated levels of tau in cerebrospinal fluid and the APOE epsilon4/epsilon4 genotype. Dement Geriatr Cogn Disord 27, 458-464.
32. Devanand DP, Pelton GH, Zamora D, Liu X, Tabert MH, Goodkind M, Scarmeas N, Braun I, SternY, MayeuxR(2005) Predictive utility of apolipoprotein E genotype for Alzheimer disease in outpatients with mild cognitive impairment. Arch Neurol 62, 975-980.
33. Hamalainen A, Grau-Olivares M, Tervo S, Niskanen E, Pennanen C, Huuskonen J, Kivipelto M, Hanninen T, Tapiola M, Vanhanen M, Hallikainen M, Helkala EL, Nissinen A, Vanninen RL, Soininen H (2008) Apolipoprotein E epsilon 4 allele is associated with increased atrophy in progressive mild cognitive impairment: a voxel-based morphometric study. Neurodegener Dis 5, 186-189.
34. Hsiung GY, Sadovnick AD, Feldman H (2004) Apolipoprotein E epsilon4 genotype as a risk factor for cognitive decline and dementia: data from the Canadian Study of Health and Aging. CMAJ 171, 863-867.
35. Jack CR, Jr., Petersen RC, Xu YC, O'Brien PC, Smith GE, Ivnik RJ, Boeve BF, Waring SC, Tangalos EG, Kokmen E (1999) Prediction of AD with MRI-based hippocampal volume in mild cognitive impairment. Neurology 52, 1397-1403.
36. Ramakers IH, Visser PJ, Aalten P, Bekers O, Sleegers K, van Broeckhoven CL, Jolles J, Verhey FR (2008) The association between APOE genotype and memory dysfunction in subjects with mild cognitive impairment is related to age and Alzheimer pathology. Dement Geriatr Cogn Disord 26, 101-108.
37. Tierney MC, Szalai JP, SnowWG,Fisher RH, TsudaT, Chi H, McLachlan DR, St George-Hyslop PH (1996) A prospective study of the clinical utility of ApoE genotype in the prediction of outcome in patients with memory impairment. Neurology 46, 149-154.
38. Slooter AJ, Cruts M, Kalmijn S, Hofman A, Breteler MM, Van Broeckhoven C, van Duijn CM (1998) Risk estimates of dementia by apolipoprotein E genotypes from a populationbased incidence study: the Rotterdam Study. Arch Neurol 55, 964-968.
39. Ashford JW, Mortimer JA (2002) Non-familial Alzheimer's disease is mainly due to genetic factors. J Alzheimers Dis 4, 169-177.
40. Strittmatter WJ, Weisgraber KH, Huang DY, Dong LM, Salvesen GS, Pericak-Vance M, Schmechel D, Saunders AM, Goldgaber D, Roses AD (1993) Binding of human apolipoprotein E to synthetic amyloid beta peptide: isoformspecific effects and implications for late-onset Alzheimer disease. Proc Natl Acad Sci U S A 90, 8098-8102.
41. Schmechel DE, Saunders AM, Strittmatter WJ, Crain BJ, Hulette CM, Joo SH, Pericak-Vance MA, Goldgaber D, Roses AD (1993) Increased amyloid beta-peptide deposition in cerebral cortex as a consequence of apolipoprotein E genotype in late-onset Alzheimer disease. Proc Natl Acad Sci U S A 90, 9649-9653.
42. Rebeck GW, Reiter JS, Strickland DK, Hyman BT (1993) Apolipoprotein E in sporadic Alzheimer's disease: allelic variation and receptor interactions. Neuron 11, 575-580.
43. Bales KR, Verina T, Cummins DJ, Du Y, Dodel RC, Saura J, Fishman CE, DeLong CA, Piccardo P, Petegnief V, Ghetti B, Paul SM (1999) Apolipoprotein E is essential for amyloid deposition in the APP(V717F) transgenic mouse model of Alzheimer's disease. Proc Natl Acad Sci U S A 96, 15233-15238.
44. Bales KR, Verina T, Dodel RC, Du Y, Altstiel L, Bender M, Hyslop P, Johnstone EM, Little SP, Cummins DJ, Piccardo P, Ghetti B, Paul SM (1997) Lack of apolipoprotein E dramatically reduces amyloid beta-peptide deposition. Nat Genet 17, 263-264.
45. Kindy MS, Rader DJ (1998) Reduction in amyloid Aamyloid formation in apolipoprotein-E-deficient mice. Am J Pathol 152, 1387-1395.
46. Ma J, Yee A, Brewer HB, Jr., Das S, Potter H (1994) Amyloid-associated proteins alpha 1-antichymotrypsin and apolipoprotein E promote assembly of Alzheimer betaprotein into filaments. Nature 372, 92-94.
47. Sanan DA, Weisgraber KH, Russell SJ, Mahley RW, Huang D, Saunders A, Schmechel D, Wisniewski T, Frangione B, Roses AD, et al. (1994) Apolipoprotein E associates with beta amyloid peptide of Alzheimer's disease to form novel monofibrils. Isoform apoE4 associates more efficiently than apoE3. J Clin Invest 94, 860-869.
48. Holtzman DM, Bales KR, Tenkova T, Fagan AM, Parsadanian M, Sartorius LJ, Mackey B, Olney J, McKeel D, Wozniak D, Paul SM (2000) Apolipoprotein E isoform-dependent amyloid deposition and neuritic degeneration in a mouse model of Alzheimer's disease. Proc Natl Acad Sci U S A 97, 2892-2897.
49. Holtzman DM, Bales KR, Wu S, Bhat P, Parsadanian M, Fagan AM, Chang LK, Sun Y, Paul SM (1999) Expression of human apolipoprotein E reduces amyloid-beta deposition in a mouse model of Alzheimer's disease. J Clin Invest 103, R15-R21.
50. Sparks DL, Scheff SW, Hunsaker JC, 3rd, Liu H, Landers T, Gross DR (1994) Induction of Alzheimer-like beta-amyloid immunoreactivity in the brains of rabbits with dietary cholesterol. Exp Neurol 126, 88-94.
51. Refolo LM, Malester B, LaFrancois J, Bryant-Thomas T, Wang R, Tint GS, Sambamurti K, Duff K, Pappolla MA (2000) Hypercholesterolemia accelerates the Alzheimer's amyloid pathology in a transgenic mouse model. Neurobiol Dis 7, 321-331.
52. Bodovitz S, Klein WL (1996) Cholesterol modulates alphasecretase cleavage of amyloid precursor protein. J Biol Chem 271, 4436-4440.
53. Howland DS, Trusko SP, Savage MJ, Reaume AG, Lang DM, Hirsch JD, Maeda N, Siman R, Greenberg BD, Scott RW, Flood DG (1998) Modulation of secreted beta-amyloid precursor protein and amyloid beta-peptide in brain by cholesterol. J Biol Chem 273, 16576-16582.
54. Farrer LA, Cupples LA, Haines JL, Hyman B, Kukull WA, Mayeux R, Myers RH, Pericak-Vance MA, Risch N, van Duijn CM (1997) Effects of age, sex, and ethnicity on the association between apolipoprotein E genotype and Alzheimer disease. A meta-analysis. APOE and Alzheimer Disease Meta Analysis Consortium. JAMA 278, 1349-1356.
55. Gozal D, Capdevila OS, Kheirandish-Gozal L, Crabtree VM (2007) APOE epsilon 4 allele, cognitive dysfunction, and obstructive sleep apnea in children. Neurology 69, 243-249. (Pubitemid 47205685)
56. Caselli RJ, Graff-Radford NR, Reiman EM, Weaver A, Osborne D, Lucas J, Uecker A, Thibodeau SN (1999) Preclinical memory decline in cognitively normal apolipoprotein E-epsilon4 homozygotes. Neurology 53, 201-207.
57. Flory JD, Manuck SB, Ferrell RE, Ryan CM, Muldoon MF (2000) Memory performance and the apolipoprotein E polymorphism in a community sample of middle-aged adults. Am J Med Genet 96, 707-711.
58. Liu F, Pardo LM, Schuur M, Sanchez-Juan P, Isaacs A, Sleegers K, de Koning I, Zorkoltseva IV, Axenovich TI,Witteman JC, Janssens AC, van Swieten JC, Aulchenko YS, Oostra BA, van Duijn CM (2008) The apolipoprotein E gene and its age-specific effects on cognitive function. Neurobiol Aging, in press.
59. Schultz MR, Lyons MJ, Franz CE, Grant MD, Boake C, Jacobson KC, Xian H, Schellenberg GD, Eisen SA, Kremen WS (2008) Apolipoprotein E genotype and memory in the sixth decade of life. Neurology 70, 1771-1777.
60. Wehling E, Lundervold AJ, Standnes B, Gjerstad L, Reinvang I (2007) APOE status and its association to learning and memory performance in middle aged and older Norwegians seeking assessment for memory deficits. Behav Brain Funct 3, 57.
61. Mak YT, Chiu H, Woo J, Kay R, Chan YS, Hui E, Sze KH, Lum C, Kwok T, Pang CP (1996) Apolipoprotein E genotype and Alzheimer's disease in Hong Kong elderly Chinese. Neurology 46, 146-149. (Pubitemid 26156120)
62. Hallman DM, Boerwinkle E, Saha N, Sandholzer C, Menzel HJ, Csazar A, UtermannG(1991) The apolipoprotein E polymorphism: a comparison of allele frequencies and effects in nine populations. Am J Hum Genet 49, 338-349.
63. do Couto FS, de Mendonca A, Garcia C, Rocha L, Lechner MC (1998) Age of onset in patients with Alzheimer's disease with different apoE genotypes. J Neurol Neurosurg Psychiatry 64, 817.
64. Dal Forno G, Rasmusson DX, Brandt J, Carson KA, Brookmeyer R, Troncoso J, Kawas CH (1996) Apolipoprotein E genotype and rate of decline in probable Alzheimer's disease. Arch Neurol 53, 345-350. (Pubitemid 26110090)
65. Welsh-Bohmer KA, Ostbye T, Sanders L, Pieper CF, Hayden KM, Tschanz JT, Norton MCFTCCSG(2008) Neuropsychological performance in advanced age: Influences of Demographic factors and Apolipoprotein E: Findings from the Cache County Memory Study. Clin Neuropsychol, 1-23.
66. Salo A, Ylikoski R, Verkkoniemi A, Polvikoski T, Juva K, Rastas S, Kontula K, Kainulainen K, Niinisto L, Notkola IL, Sulkava R (2001) Does apolipoprotein E influence learning and memory in the nondemented oldest old? Int Psychogeriatr 13, 451-459.
67. Murphy GM, Jr., Taylor J, Kraemer HC, Yesavage J, Tinklenberg JR (1997) No association between apolipoprotein E epsilon 4 allele and rate of decline in Alzheimer's disease. Am J Psychiatry 154, 603-608. (Pubitemid 27197591)
68. Cosentino S, Scarmeas N, Helzner E, Glymour MM, Brandt J, Albert M, Blacker D, Stern Y (2008) APOE epsilon 4 allele predicts faster cognitive decline in mild Alzheimer disease. Neurology 70, 1842-1849.
69. Hirono N, Hashimoto M, Yasuda M, Kazui H, Mori E (2003) Accelerated memory decline in Alzheimer's disease with apolipoprotein epsilon4 allele. J Neuropsychiatry Clin Neurosci 15, 354-358.
70. Mayeux R, Small SA, Tang M, Tycko B, Stern Y (2001) Memory performance in healthy elderly without Alzheimer's disease: effects of time and apolipoprotein-E. Neurobiol Aging 22, 683-689.
71. Wilson RS, Bienias JL, Berry-Kravis E, Evans DA, Bennett DA (2002) The apolipoprotein E epsilon 2 allele and decline in episodic memory. J Neurol Neurosurg Psychiatry 73, 672-677.
72. Lehmann DJ, Refsum H, Nurk E, Warden DR, Tell GS, Vollset SE, Engedal K, Nygaard HA, Smith AD (2006) Apolipoprotein E epsilon4 and impaired episodic memory in community-dwelling elderly people: a marked sex difference. The Hordaland Health Study. J Neurol Neurosurg Psychiatry 77, 902-908.
73. Bondi MW, Salmon DP, Monsch AU, Galasko D, Butters N, Klauber MR, Thal LJ, Saitoh T (1995) Episodic memory changes are associated with the APOE-epsilon 4 allele in nondemented older adults. Neurology 45, 2203-2206.
74. Dik MG, Jonker C, Comijs HC, Bouter LM, Twisk JW, van Kamp GJ, Deeg DJ (2001) Memory complaints and APOEepsilon4 accelerate cognitive decline in cognitively normal elderly. Neurology 57, 2217-2222.
75. Reynolds CA, Prince JA, Feuk L, Brookes AJ, Gatz M, Pedersen NL (2006) Longitudinal memory performance during normal aging: twin association models of APOE and other Alzheimer candidate genes. Behav Genet 36, 185-194.
76. Saunders AM, Hulette O, Welsh-Bohmer KA, Schmechel DE, Crain B, Burke JR, Alberts MJ, Strittmatter WJ, Breitner JC, Rosenberg C (1996) Specificity, sensitivity, and predictive value of apolipoprotein-E genotyping for sporadic Alzheimer's disease. Lancet 348, 90-93.
77. Mayeux R, Saunders AM, Shea S, Mirra S, Evans D, Roses AD, Hyman BT, Crain B, Tang MX, Phelps CH (1998) Utility of the apolipoprotein E genotype in the diagnosis of Alzheimer's disease. Alzheimer's Disease Centers Consortium on Apolipoprotein E and Alzheimer's Disease. N Engl J Med 338, 506-511. (Pubitemid 28103134)
78. Roses AD (1995) Apolipoprotein E genotyping in the differential diagnosis, not prediction, of Alzheimer's disease. Ann Neurol 38, 6-14.
79. Slooter AJ, Breteler MB, Ott A, Van Broeckhoven C, van Duijn CM (1996) APOE genotyping in differential diagnosis of Alzheimer's disease. Lancet 348, 334.
80. Kakulas BA, Wilton SD, Fabian VA, Jones TM (1996) Apolipoprotein-E genotyping in diagnosis of Alzheimer's disease. Lancet 348, 483.
81. Edbauer D,Winkler E, Regula JT, Pesold B, Steiner H, Haass C (2003) Reconstitution of gamma-secretase activity. Nat Cell Biol 5, 486-488.
82. Cobbold C, Monaco AP, Sivaprasadarao A, Ponnambalam S (2003) Aberrant trafficking of transmembrane proteins in human disease. Trends Cell Biol 13, 639-647.
83. Harter C, Reinhard C (2000) The secretory pathway from history to the state of the art. Subcell Biochem 34, 1-38.
84. Le Borgne R, Hoflack B (1998) Protein transport from the secretory to the endocytic pathway in mammalian cells. Biochim Biophys Acta 1404, 195-209.
85. Chen WJ, Goldstein JL, Brown MS (1990) NPXY, a sequence often found in cytoplasmic tails, is required for coated pit-mediated internalization of the low density lipoprotein receptor. J Biol Chem 265, 3116-3123.
86. He X, Li F, Chang WP, Tang J (2005) GGA proteins mediate the recycling pathway of memapsin 2 (BACE). J Biol Chem 280, 11696-11703.
87. Small SA, Gandy S (2006) Sorting through the cell biology of Alzheimer's disease: intracellular pathways to pathogenesis. Neuron 52, 15-31.
88. Traub LM (2005) Common principles in clathrin-mediated sorting at the Golgi and the plasma membrane. Biochim Biophys Acta 1744, 415-437.
89. Rogaeva E, MengY, Lee JH, GuY, Kawarai T, Zou F, Katayama T, Baldwin CT, Cheng R, Hasegawa H, Chen F, Shibata N, Lunetta KL, Pardossi-Piquard R, Bohm C, Wakutani Y, Cupples LA, Cuenco KT, Green RC, Pinessi L, Rainero I, Sorbi S, Bruni A, Duara R, Friedland RP, Inzelberg R, Hampe W, Bujo H, Song YQ, Andersen OM, Willnow TE, Graff-Radford N, Petersen RC, Dickson D, Der SD, Fraser PE, Schmitt-Ulms G, Younkin S, Mayeux R, Farrer LA, St George-Hyslop P (2007) The neuronal sortilin-related receptor SORL1 is genetically associated with Alzheimer disease. Nat Genet 39, 168-177.
90. Andersen OM, Reiche J, Schmidt V, Gotthardt M, Spoelgen R, Behlke J, von Arnim CA, Breiderhoff T, Jansen P, Wu X, Bales KR, Cappai R, Masters CL, Gliemann J, Mufson EJ, Hyman BT, Paul SM, Nykjaer A, Willnow TE (2005) Neuronal sorting protein-related receptor sorLA/LR11 regulates processing of the amyloid precursor protein. Proc Natl Acad Sci U S A 102, 13461-13466.
91. Andersen OM, SchmidtV, Spoelgen R, Gliemann J, Behlke J, Galatis D, McKinstry WJ, Parker MW, Masters CL, Hyman BT, Cappai R, Willnow TE (2006) Molecular dissection of the interaction between amyloid precursor protein and its neuronal trafficking receptor SorLA/LR11. Biochemistry 45, 2618-2628.
92. Clewes O, Fahey MS, Tyler SJ, Watson JJ, Seok H, Catania C, Cho K, Dawbarn D, Allen SJ (2008) Human ProNGF: biological effects and binding profiles at TrkA, P75NTR and sortilin. J Neurochem 107, 1124-1135.
93. Nykjaer A, Lee R, Teng KK, Jansen P, Madsen P, Nielsen MS, Jacobsen C, Kliemannel M, Schwarz E, Willnow TE, Hempstead BL, Petersen CM (2004) Sortilin is essential for proNGF-induced neuronal cell death. Nature 427, 843-848.
94. Bettens K, Brouwers N, Engelborghs S, De Deyn PP, Van Broeckhoven C, Sleegers K (2008) SORL1 is genetically associated with increased risk for late-onset Alzheimer disease in the Belgian population. Hum Mutat 29, 769-770.
95. Lee JH, Cheng R, Honig LS,Vonsattel JP, Clark L, Mayeux R (2008) Association between genetic variants in SORL1 and autopsy-confirmed Alzheimer disease. Neurology 70, 887-889.
96. Lee JH, Cheng R, Schupf N, Manly J, Lantigua R, Stern Y, Rogaeva E, Wakutani Y, Farrer L, St George-Hyslop P, Mayeux R (2007) The association between genetic variants in SORL1 and Alzheimer disease in an urban, multiethnic, community-based cohort. Arch Neurol 64, 501-506.
97. Meng Y, Lee JH, Cheng R, St George-Hyslop P, Mayeux R, Farrer LA (2007) Association between SORL1 and Alzheimer's disease in a genome-wide study. Neuroreport 18, 1761-1764. (Pubitemid 350303747)
98. Seshadri S, DeStefano AL, Au R, Massaro JM, Beiser AS, Kelly-Hayes M, Kase CS, D'Agostino RB, Sr., Decarli C, Atwood LD, Wolf PA (2007) Genetic correlates of brain aging on MRI and cognitive test measures: a genome-wide association and linkage analysis in the Framingham Study. BMC Med Genet 8 Suppl 1, S15.
99. Tan EK, Lee J, Chen CP, Teo YY, Zhao Y, Lee WL (2009) SORL1 haplotypes modulate risk of Alzheimer's disease in Chinese. Neurobiol Aging 30, 1048-1051.
100. Kolsch H, Jessen F, Wiltfang J, Lewczuk P, Dichgans M, Teipel SJ, Kornhuber J, Frolich L, Heuser I, Peters O,Wiese B, Kaduszkiewicz H, van den Bussche H, Hull M, Kurz A, Ruther E, Henn FA, Maier W (2009) Association of SORL1 gene variants with Alzheimer's disease. Brain Res 1264, 1-6.
101. Li H, Wetten S, Li L, St Jean PL, Upmanyu R, Surh L, Hosford D, Barnes MR, Briley JD, Borrie M, Coletta N, Delisle R, Dhalla D, Ehm MG, Feldman HH, Fornazzari L, Gauthier S, Goodgame N, Guzman D, Hammond S, Hollingworth P, Hsiung GY, Johnson J, Kelly DD, Keren R, Kertesz A, King KS, Lovestone S, Loy-English I, Matthews PM, Owen MJ, Plumpton M, Pryse-Phillips W, Prinjha RK, Richardson JC, Saunders A, Slater AJ, St George-Hyslop PH, Stinnett SW, Swartz JE, Taylor RL, Wherrett J, Williams J, Yarnall DP, Gibson RA, Irizarry MC, Middleton LT, Roses AD(2008) Candidate single-nucleotide polymorphisms from a genomewide association study of Alzheimer disease. Arch Neurol 65, 45-53.
102. Li Y, Rowland C, Catanese J, Morris J, Lovestone S, O'Donovan MC, Goate A, Owen M, Williams J, Grupe A (2008) SORL1 variants and risk of late-onset Alzheimer's disease. Neurobiol Dis 29, 293-296.
103. Webster JA, Myers AJ, Pearson JV, Craig DW, Hu-Lince D, Coon KD, Zismann VL, Beach T, Leung D, Bryden L, Halperin RF, Marlowe L, Kaleem M, Huentelman MJ, Joshipura K,Walker D, Heward CB, Ravid R, Rogers J, Papassotiropoulos A, Hardy J, Reiman EM, Stephan DA (2008) Sorl1 as an Alzheimer's disease predisposition gene? Neurodegener Dis 5, 60-64.
104. Houlihan LM, Harris SE, Luciano M, Gow AJ, Starr JM, Visscher PM, Deary IJ (2009) Replication study of candidate genes for cognitive abilities: the Lothian Birth Cohort 1936. Genes Brain Behav 8, 238-247.
105. Minster RL,DeKosky ST, Kamboh MI (2008) No association of SORL1 SNPs with Alzheimer's disease. Neurosci Lett 440, 190-192.
106. Shibata N, Ohnuma T, Baba H, Higashi S, Nishioka K, Arai H (2008) Genetic association between SORL1 polymorphisms and Alzheimer's disease in a Japanese population. Dement Geriatr Cogn Disord 26, 161-164.
107. Lee JH, Shibata N, Cheng R, Mayeux R (2008) Possible Association between SORL1 and Alzheimer Disease?. Reanalysing the Data of Shibata et al. Dement Geriatr Cogn Disord 26, 482.
108. Sager KL,Wuu J, Leurgans SE, Rees HD, Gearing M, Mufson EJ, Levey AI, Lah JJ (2007) Neuronal LR11/sorLA expression is reduced in mild cognitive impairment. Ann Neurol 62, 640-647.
109. Bertram L, McQueen MB, Mullin K, Blacker D, Tanzi RE (2007) Systematic meta-analyses of Alzheimer disease genetic association studies: the AlzGene database. Nat Genet 39, 17-23.
110. Grupe A, Abraham R, Li Y, Rowland C, Hollingworth P, Morgan A, Jehu L, Segurado R, Stone D, Schadt E, Karnoub M, Nowotny P, Tacey K, Catanese J, Sninsky J, Brayne C, Rubinsztein D, Gill M, Lawlor B, Lovestone S, Holmans P, O'Donovan M, Morris JC, Thal L, Goate A, Owen MJ, Williams J (2007) Evidence for novel susceptibility genes for late-onset Alzheimer's disease from a genome-wide association study of putative functional variants. Hum Mol Genet 16, 865-873. (Pubitemid 47064316)
111. Holmans P, Hamshere M, Hollingworth P, Rice F, Tunstall N, Jones S, Moore P, Wavrant DeVrieze F, Myers A, Crook R, Compton D, Marshall H, Meyer D, Shears S, Booth J, Ramic D, Williams N, Norton N, Abraham R, Kehoe P, Williams H, Rudrasingham V, O'Donovan M, Jones L, Hardy J, Goate A, Lovestone S, Owen M,Williams J (2005) Genome screen for loci influencing age at onset and rate of decline in late onset Alzheimer's disease. Am J Med Genet B Neuropsychiatr Genet 135, 24-32.
112. Liu F, Arias-Vasquez A, Sleegers K, Aulchenko YS, Kayser M, Sanchez-Juan P, Feng BJ, Bertoli-Avella AM,van Swieten J, Axenovich TI, Heutink P, van Broeckhoven C, Oostra BA, van Duijn CM (2007) A genomewide screen for late-onset Alzheimer disease in a genetically isolated dutch population. Am J Hum Genet 81, 17-31.
113. Myers A, Wavrant De-Vrieze F, Holmans P, Hamshere M, Crook R, Compton D, Marshall H, Meyer D, Shears S, Booth J, Ramic D, Knowles H, Morris JC, Williams N, Norton N, Abraham R, Kehoe P, Williams H, Rudrasingham V, Rice F, Giles P, Tunstall N, Jones L, Lovestone S, Williams J, Owen MJ, Hardy J, Goate A (2002) Full genome screen for Alzheimer disease: stage II analysis. Am J Med Genet 114, 235-244.
114. Dreses-Werringloer U, Lambert JC, Vingtdeux V, Zhao H, Vais H, Siebert A, Jain A, Koppel J, Rovelet-Lecrux A, Hannequin D, Pasquier F, Galimberti D, Scarpini E, Mann D, Lendon C, Campion D, Amouyel P, Davies P, Foskett JK, Campagne F, Marambaud P (2008) A polymorphism in CALHM1 influences Ca2+ homeostasis, Abeta levels, and Alzheimer's disease risk. Cell 133, 1149-1161.
115. Reiman EM, Webster JA, Myers AJ, Hardy J, Dunckley T, Zismann VL, Joshipura KD, Pearson JV, Hu-Lince D, Huentelman MJ, Craig DW, Coon KD, Liang WS, Herbert RH, Beach T, Rohrer KC, Zhao AS, Leung D, Bryden L, Marlowe L, Kaleem M, Mastroeni D, Grover A, Heward CB, Ravid R, Rogers J, Hutton ML, Melquist S, Petersen RC, Alexander GE, Caselli RJ, Kukull W, Papassotiropoulos A, Stephan DA (2007) GAB2 alleles modify Alzheimer's risk in APOE epsilon4 carriers. Neuron 54, 713-720.
116. McIlroy SP, Crawford VL, Dynan KB, McGleenon BM, Vahidassr MD, Lawson JT, Passmore AP (2000) Butyrylcholinesterase K variant is genetically associated with late onset Alzheimer's disease in Northern Ireland. J Med Genet 37, 182-185.
117. Bartels CF, Jensen FS, Lockridge O, van der Spek AF, Rubinstein HM, Lubrano T, La Du BN (1992) DNA mutation associated with the human butyrylcholinesterase K-variant and its linkage to the atypical variant mutation and other polymorphic sites. Am J Hum Genet 50, 1086-1103.
118. De FerrariGV, Papassotiropoulos A, BiecheleT,Wavrant De- Vrieze F, Avila ME, Major MB, Myers A, Saez K, Henriquez JP, Zhao A, Wollmer MA, Nitsch RM, Hock C, Morris CM, Hardy J, Moon RT (2007) 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 104, 9434-9439.
119. Blacker D,Wilcox MA, Laird NM, Rodes L, Horvath SM, Go RC, Perry R,Watson B, Jr., Bassett SS, McInnis MG, Albert MS, Hyman BT, Tanzi RE (1998) Alpha-2 macroglobulin is genetically associated with Alzheimer disease. Nat Genet 19, 357-360.
120. Giedraitis V, Hedlund M, Skoglund L, Blom E, Ingvast S, Brundin R, Lannfelt L, Glaser A (2006) New Alzheimer's disease locus on chromosome 8. J Med Genet 43, 931-935.
121. Li Y, Nowotny P, Holmans P, Smemo S, Kauwe JS, Hinrichs AL, Tacey K, Doil L, van Luchene R, Garcia V, Rowland C, Schrodi S, Leong D, Gogic G, Chan J, Cravchik A, Ross D, Lau K, Kwok S, Chang SY, Catanese J, Sninsky J, White TJ, Hardy J, Powell J, Lovestone S, Morris JC, Thal L, Owen M,Williams J, Goate A, Grupe A (2004) Association of lateonset Alzheimer's disease with genetic variation in multiple members of the GAPD gene family. Proc Natl Acad Sci U S A 101, 15688-15693.
122. Ozturk A, Desai PP, Minster RL, Dekosky ST, Kamboh MI (2005) Three SNPs in the GSTO1, GSTO2 and PRSS11 genes on chromosome 10 are not associated with age-at-onset of Alzheimer's disease. Neurobiol Aging 26, 1161-1165.
123. Bertram L, Hiltunen M, Parkinson M, Ingelsson M, Lange C, Ramasamy K, Mullin K, Menon R, Sampson AJ, Hsiao MY, Elliott KJ, Velicelebi G, Moscarillo T, Hyman BT,Wagner SL, Becker KD, Blacker D, Tanzi RE (2005) Familybased association between Alzheimer's disease and variants in UBQLN1. N Engl J Med 352, 884-894. (Pubitemid 40300297)
124. Blacker D, Bertram L, Saunders AJ, Moscarillo TJ, Albert MS, Wiener H, Perry RT, Collins JS, Harrell LE, Go RC, Mahoney A, Beaty T, Fallin MD, Avramopoulos D, Chase GA, Folstein MF, McInnis MG,Bassett SS, Doheny KJ, Pugh EW, Tanzi RE (2003) Results of a high-resolution genome screen of 437 Alzheimer's disease families. Hum Mol Genet 12, 23-32.
125. Farrer LA, Bowirrat A, Friedland RP, Waraska K, Korczyn AD, Baldwin CT (2003) Identification of multiple loci for Alzheimer disease in a consanguineous Israeli-Arab community. Hum Mol Genet 12, 415-422.
126. Hahs DW, McCauley JL, Crunk AE, McFarland LL, Gaskell PC, Jiang L, Slifer SH, Vance JM, Scott WK,Welsh-Bohmer KA, Johnson SR, Jackson CE, Pericak-Vance MA, Haines JL (2006) A genome-wide linkage analysis of dementia in the Amish. Am J Med Genet B Neuropsychiatr Genet 141, 160-166.
127. Lee JH, Cheng R, Santana V, Williamson J, Lantigua R, Medrano M, Arriaga A, Stern Y, Tycko B, Rogaeva E,Wakutani Y, Kawarai T, St George-Hyslop P, Mayeux R (2006) Expanded genomewide scan implicates a novel locus at 3q28 among Caribbean hispanics with familial Alzheimer disease. Arch Neurol 63, 1591-1598.
128. Pericak-Vance MA, Grubber J, Bailey LR, Hedges D,West S, Santoro L, Kemmerer B, Hall JL, Saunders AM, Roses AD, Small GW, Scott WK, Conneally PM, Vance JM, Haines JL (2000) Identification of novel genes in late-onset Alzheimer's disease. Exp Gerontol 35, 1343-1352.
129. Rademakers R, Cruts M, Sleegers K, Dermaut B, Theuns J, Aulchenko Y, Weckx S, De Pooter T, Van den Broeck M, Corsmit E, De Rijk P, Del-Favero J, van Swieten J, van Duijn CM, Van Broeckhoven C (2005) Linkage and association studies identify a novel locus for Alzheimer disease at 7q36 in a Dutch population-based sample. Am J Hum Genet 77, 643-652.
130. Scott WK, Hauser ER, Schmechel DE, Welsh-Bohmer KA, Small GW, Roses AD, Saunders AM, Gilbert JR, Vance JM, Haines JL, Pericak-Vance MA (2003) Ordered-subsets linkage analysis detects novel Alzheimer disease loci on chromosomes 2q34 and 15q22. Am J Hum Genet 73, 1041-1051.
131. Li M, Atmaca-Sonmez P, Othman M, Branham KE, Khanna R, Wade MS, Li Y, Liang L, Zareparsi S, Swaroop A, Abecasis GR (2006) CFH haplotypes without the Y402H coding variant show strong association with susceptibility to age-related macular degeneration. Nat Genet 38, 1049-1054.
132. Sweet RA, Nimgaonkar VL, Devlin B, Jeste DV (2003) Psychotic symptoms in Alzheimer disease: evidence for a distinct phenotype. Mol Psychiatry 8, 383-392.
133. Wijsman EM, Daw EW, Yu CE, Payami H, Steinbart EJ, Nochlin D, Conlon EM, Bird TD, Schellenberg GD (2004) Evidence for a novel late-onset Alzheimer disease locus on chromosome 19p13.2. Am J Hum Genet 75, 398-409. (Pubitemid 39095816)
134. Arosio B, Segat L, Milanese M, Galimberti L, Calabresi C, Zanetti M, Trabattoni D, Annoni G, Crovella S, Vergani C (2007) PIN-1 promoter polymorphisms in mild cognitive impairment and susceptibility to Alzheimer's disease: a preliminary report. Aging Clin Exp Res 19, 406-409.
135. Barabash A, Marcos A, Ancin I, Vazquez-Alvarez B, de Ugarte C, Gil P, Fernandez C, Encinas M, Lopez-Ibor JJ, Cabranes JA (2009) APOE, ACT and CHRNA7 genes in the conversion from amnestic mild cognitive impairment to Alzheimer's disease. Neurobiol Aging 30, 1254-1264.
136. Arosio B, Bergamaschini L, Galimberti L, La Porta C, Zanetti M, Calabresi C, Scarpini E, Annoni G, Vergani C (2007) +10 T/C polymorphisms in the gene of transforming growth factor-beta1 are associated with neurodegeneration and its clinical evolution. Mech Ageing Dev 128, 553-557.
137. Chiappelli M, Borroni B, Archetti S, Calabrese E, Corsi MM, Franceschi M, Padovani A, Licastro F (2006) VEGF gene and phenotype relation with Alzheimer's disease and mild cognitive impairment. Rejuvenation Res 9, 485-493.
138. Fernandez Del Pozo V, Alvarez Alvarez M, Fernandez Martinez M, Galdos Alcelay L, Gomez Busto F, Pena JA, Alfonso-Sanchez MA, Zarranz Imirizaldu JJ, de Pancorbo MM (2006) Polymorphism in the cholesterol 24Shydroxylase gene (CYP46A1) associated with the APOEpsilon3 allele increases the risk of Alzheimer's disease and of mild cognitive impairment progressing to Alzheimer's disease. Dement Geriatr Cogn Disord 21, 81-87.
139. Sole-Padulles C, Bartres-Faz D, Junque C, Via M, Matarin M, Gonzalez-Perez E, Moral P, Moya A, Clemente IC (2004) Poorer cognitive performance in humans with mild cognitive impairment carrying the T variant of the Glu/Asp NOS3 polymorphism. Neurosci Lett 358, 5-8.
140. Ertekin-Taner N, Ronald J, Feuk L, Prince J, Tucker M, Younkin L, Hella M, Jain S, Hackett A, Scanlin L, Kelly J, Kihiko-Ehman M, Neltner M, Hersh L, Kindy M, Markesbery W, Hutton M, de Andrade M, Petersen RC, Graff- Radford N, Estus S, Brookes AJ, Younkin SG (2005) Elevated amyloid beta protein (Abeta42) and late onset Alzheimer's disease are associated with single nucleotide polymorphisms in the urokinase-type plasminogen activator gene. Hum Mol Genet 14, 447-460.
141. Ertekin-Taner N, Allen M, Fadale D, Scanlin L, Younkin L, Petersen RC, Graff-Radford N, Younkin SG (2004) Genetic variants in a haplotype block spanning IDE are significantly associated with plasma Abeta42 levels and risk for Alzheimer disease. Hum Mutat 23, 334-342.
142. FarrisW, Mansourian S, Leissring MA, Eckman EA, Bertram L, Eckman CB, Tanzi RE, Selkoe DJ (2004) Partial loss-offunction mutations in insulin-degrading enzyme that induce diabetes also impair degradation of amyloid beta-protein. Am J Pathol 164, 1425-1434.
143. Daw EW, Heath SC, Wijsman EM (1999) Multipoint oligogenic analysis of age-at-onset data with applications to Alzheimer disease pedigrees. Am J Hum Genet 64, 839-851.
144. Daw EW, Payami H, Nemens EJ, Nochlin D, Bird TD, Schellenberg GD,Wijsman EM (2000) The number of trait loci in late-onset Alzheimer disease. Am J Hum Genet 66, 196-204.
145. Gottesman, II, Gould TD (2003) The endophenotype concept in psychiatry: etymology and strategic intentions. Am J Psychiatry 160, 636-645.
146. Blangero J, Williams JT, Almasy L (2003) Novel familybased approaches to genetic risk in thrombosis. J Thromb Haemost 1, 1391-1397.
147. Lehtovirta M, Helisalmi S, Mannermaa A, Soininen H, Koivisto K, Ryynanen M, Riekkinen P, Sr. (1995) Apolipoprotein E polymorphism and Alzheimer's disease in eastern Finland. Neurosci Lett 185, 13-15.
148. Geschwind DH, Miller BL, DeCarli C, Carmelli D (2002) Heritability of lobar brain volumes in twins supports genetic models of cerebral laterality and handedness. Proc Natl Acad Sci U S A 99, 3176-3181.
149. Dik MG, Jonker C, Bouter LM, Geerlings MI, van Kamp GJ, Deeg DJ (2000) APOE-epsilon4 is associated with memory decline in cognitively impaired elderly. Neurology 54, 1492-1497. (Pubitemid 30210473)
150. Small BJ, Graves AB, McEvoy CL, Crawford FC, Mullan M, Mortimer JA (2000) Is APOE-epsilon4 a risk factor for cognitive impairment in normal aging? Neurology 54, 2082-2088.
151. Farlow MR, He Y, Tekin S, Xu J, Lane R, Charles HC (2004) Impact of APOE in mild cognitive impairment. Neurology 63, 1898-1901. (Pubitemid 39532387)
152. Kleiman T, Zdanys K, Black B, Rightmer T, GreyM, Garman K,Macavoy M, Gelernter J, van Dyck C (2006) Apolipoprotein E epsilon4 allele is unrelated to cognitive or functional decline in Alzheimer's disease: retrospective and prospective analysis. Dement Geriatr Cogn Disord 22, 73-82.
153. Caselli RJ, Reiman EM, Locke DE, Hutton ML, Hentz JG, Hoffman-Snyder C,Woodruff BK, Alexander GE, OsborneD (2007) Cognitive domain decline in healthy apolipoprotein E epsilon4 homozygotes before the diagnosis of mild cognitive impairment. Arch Neurol 64, 1306-1311.
154. AggarwalNT,Wilson RS, Beck TL, Bienias JL, Berry-Kravis E, Bennett DA (2005) The apolipoprotein E epsilon4 allele and incident Alzheimer's disease in persons with mild cognitive impairment. Neurocase 11, 3-7.
155. Tschanz JT,Welsh-Bohmer KA, Lyketsos CG, Corcoran C, Green RC, Hayden K, Norton MC, Zandi PP, Toone L,West NA, Breitner JC (2006) Conversion to dementia from mild cognitive disorder: the Cache County Study. Neurology 67, 229-234. (Pubitemid 44305404)
156. Fleisher AS, Sowell BB, Taylor C, Gamst AC, Petersen RC, Thal LJ (2007) Clinical predictors of progression to Alzheimer disease in amnestic mild cognitive impairment. Neurology 68, 1588-1595.
157. van der Flier WM, Pijnenburg YA, Schoonenboom SN, Dik MG, Blankenstein MA, Scheltens P (2008) Distribution of APOE genotypes in a memory clinic cohort. Dement Geriatr Cogn Disord 25, 433-438.