Apolipoprotein E4: An allele associated with many diseases

Annals of Medicine

Volumn 32, Issue 2, 2000, Pages 118-127

  Smith, Jonathan D ^a  

^a ROCKEFELLER UNIVERSITY   (United States)

Author keywords

Ageing; Alzheimer's disease; Apolipoprotein E; Cardiovascular disease

Indexed keywords

APOLIPOPROTEIN E4; CHOLESTEROL;

ADULT; AGED; AGING; ALLELE; ALZHEIMER DISEASE; CARDIOVASCULAR DISEASE; CHOLESTEROL BLOOD LEVEL; COGNITIVE DEFECT; DOWN SYNDROME; FEMALE; GENE CONTROL; GENE FREQUENCY; GENETIC POLYMORPHISM; GENETIC VARIABILITY; HEAD INJURY; HUMAN; LEWY BODY; LIPOPROTEIN METABOLISM; LIPOPROTEIN SYNTHESIS; LONGEVITY; MALE; PREVALENCE; PRIORITY JOURNAL; REVIEW; STROKE; VASCULAR AMYLOIDOSIS;

EID: 0034100794     PISSN: 07853890     EISSN: None     Source Type: Journal    
DOI: 10.3109/07853890009011761     Document Type: Review

References (135)

1. Mahley RW. Apolipoprotein E: cholesterol transport protein with expanding role in cell biology. Science 1988; 240: 622-30.
2. Mahley RW, Huang Y. Apolipoprotein E: from atherosclerosis to Alzheimer's disease and beyond. Curr Opin Lipidol 1999; 10: 207-17.
3. Linton MF, Gish R, Hubl ST, Butler E, Esquivel C, Bry WI, et al. Phenotypes of apolipoprotein B and apolipoprotein E after liver transplantation. J Clin Invest 1991; 88: 270-81.
4. Boyles JK, Pitas RE, Wilson E, Mahley RW, Taylor JM. Apolipoprotein E associated with astrocytic glia of the central nervous system and with nonmyelinating glia of the peripheral nervous system. J Clin Invest 1985; 76: 1501-13.
5. Allan CM, Walker D, Segrest JP, Taylor JM. Identification and characterization of a new human gene (APOC4) in the apolipoprotein E, C-I, and C-II gene locus. Genomics 1995; 28: 291-300.
6. Utermann G, Langenbeck U, Beisiegel U, Weber W. Genetics of the apolipoprotein E system in man. Am J Hum Genet 1980; 32: 339-47.
7. Zannis VI, Just PW, Breslow JL. Human apolipoprotein E isoprotein subclasses are genetically determined. Am J Hum Genet 1981; 33: 11-24.
8. Hixson JE, Vernier DT. Restriction isotyping of human apolipoprotein E by gene amplification and cleavage with HhaI. J Lipid Res 1990; 31: 545-8.
9. Menzel HJ, Kladetzky RG, Assmann G. Apolipoprotein E polymorphism and coronary artery disease. Arteriosclerosis 1983; 3: 310-5.
10. Howard BV, Gidding SS, Liu K. Association of apolipoprotein E phenotype with plasma lipoproteins in African-American and white young adults. The CARDIA Study. Coronary Artery Risk Development in Young Adults. Am J Epidemiol 1998; 148: 859-68.
11. Zekraoui L, Lagarde JP, Raisonnier A, Gerard N, Aouizerate A, Lucotte G. High frequency of the apolipoprotein E *4 allele in African pygmies and most of the African populations in sub-Saharan Africa. Hum Biol 1997; 69: 575-81.
12. Ehnholm C, Lukka M, Kuusi T, Nikkilä E, Utermann G. Apolipoprotein E polymorphism in the Finnish population: gene frequencies and relation to lipoprotein concentrations. J Lipid Res 1986; 27: 227-35.
13. Lehtimäki T, Moilanen T, Viikari J, Åkerblom HK, Ehnholm C, Rönnemaa T, et al. Apolipoprotein E phenotypes in Finnish youths: a cross-sectional and 6-year follow-up study. J Lipid Res 1990; 31: 487-95.
14. Eggertsen G, Tegelman R, Ericsson S, Angelin B, Berglund L. Apolipoprotein E polymorphism in a healthy Swedish population: variation of allele frequency with age and relation to serum lipid concentrations. Clin Chem 1993; 39: 2125-9.
15. Evans AE, Zhang W, Moreel JF, Bard JM, Ricard S, Poirier O, et al. Polymorphisms of the apolipoprotein B and E genes and their relationship to plasma lipid variables in healthy Chinese men. Hum Genet 1993; 92: 191-7.
16. Tiret L, de Knijff P, Menzel HJ, Ehnholm C, Nicaud V, Havekes LM. ApoE polymorphism and predisposition to coronary heart disease in youths of different European populations. The EARS Study. European Atherosclerosis Research Study. Arterioscler Thromb 1994; 14: 1617-24.
17. Srinivasan SR, Ehnholm C, Wattigney W, Berenson GS. Apolipoprotein E polymorphism and its association with serum lipoprotein concentrations in black versus white children: the Bogalusa Heart Study. Metabolism 1993; 42: 381-6.
18. Cutler RG. Evolution of human longevity: a critical overview. Mech Ageing Dev 1979; 9: 337-54.
19. Herskind AM, McGue M, Holm NV, Sorensen TI, Harvald B, Vaupel JW. The heritability of human longevity: a population-based study of 2872 Danish twin pairs born 1870-900. Hum Genet 1996; 97: 319-23.
20. Robine JM, Allard M. The oldest human. Science 1998; 279: 1834-5.
21. Schachter F, Faure-Delanef L, Guenot F, Rouger H, Froguel P, Lesueur-Ginot L, et al. Genetic associations with human longevity at the apoE and ACE loci. Nat Genet 1994; 6: 29-32.
22. Ivanova R, Henon N, Lepage V, Charron D, Vicaut E, Schachter F. HLA-DR alleles display sex-dependent effects on survival and discriminate between individual and familial longevity. Hum Mol Genet 1998; 7: 187-94.
23. Louhija J, Miettinen HE, Kontula K, Tikkanen MJ, Miettinen TA, Tilvis RS. Aging and genetic variation of plasma apolipoproteins. Arterioscler Thromb 1994; 87: 1084-9.
24. Kervinen K, Savolainen MJ, Salokannel J, Hynninen A, Heikkinen J, Ehnholm C, et al. Apolipoprotein E and B polymorphisms-longevity factors assessed in nonagenarians. Atherosclerosis 1994; 105: 89-95.
25. Cauley JA, Eichner JE, Kamboh MI, Ferrell RE, Kuller LH. Apo E allele frequencies in younger (age 42-50) vs older (age 65-90) women. Genet Epidemiol 1993; 10: 27-34.
26. Jian-Gang Z, Yong-Xing M, Chuan-Fu W, Pei-Fang L, Song-Bai Z, Nui-Fan G, et al. Apolipoprotein E and longevity among Han Chinese population. Mech Ageing Dev 1998; 104: 159-67.
27. Hirose N, Homma S, Arai Y, Kawamura M, Hasegawa H, Ishida H, et al. Tokyo Centenarian Study. 4. Apolipoprotein E phenotype in Japanese centenarians living in the Tokyo metropolitan area (in Japanese). Nippon Ronen Igakkai Zasshi 1997; 34: 267-72.
28. Bader G, Zuliani G, Kostner GM, Fellin R. Apolipoprotein E polymorphism is not associated with longevity or disability in a sample of Italian octo- and nonagenarians. Gerontology 1998; 44: 293-9.
29. Thieszen SL, Hixson JE, Nagengast DJ, Wilson JE, McManus BM. Lipid phenotypes, apolipoprotein genotypes and cardiovascular risk in nonagenarians. Atherosclerosis 1990; 83: 137-46.
30. Brattstrom L, Zhang Y, Hurtig M, Refsum H, Ostensson S, Fransson L, et al. A common methylenetetrahydrofolate reductase gene mutation and longevity. Atherosclerosis 1998; 141: 315-319.
31. Bladbjerg EM, Andersen-Ranberg K, de Maat MP, Kristensen SR, Jeune B, Gram J, et al. Longevity is independent of common variations in genes associated with cardiovascular risk. Thromb Haemost 1999; 82: 1100-5.
32. Plump AS, Smith JD, Hayek T, Aalto-Setälä K, Walsh A, Verstuyft JG, et al. Severe hypercholesterolemia and atherosclerosis in apolipoprotein E-deficient mice created by homologous recombination in ES cells. Cell 1992; 71: 343-53.
33. Wilson C, Mau T, Weisgraber KH, Wardell MR, Mahley RW, Agard DA. Salt bridge relay triggers defective LDL receptor binding by a mutant apolipoprotein. Structure 1994; 2: 713-8.
34. Davignon J, Gregg RE, Sing CF. Apolipoprotein E polymorphism and atherosclerosis. Arteriosclerosis 1988; 8: 1-21.
35. Xhignesse M, Lussier-Cacan S, Sing CF, Kessling AM, Davignon J. Influences of common variants of apolipoprotein E on measures of lipid metabolism in a sample selected for health. Arterioscler Thromb 1991; 11: 1100-10.
36. Smit M, de Knijff P, Rosseneu M, Bury J, Klasen E, Frants R, et al. Apolipoprotein E polymorphism in the Netherlands and its effect on plasma lipid and apolipoprotein levels. Hum Genet 1988; 80: 287-92.
37. Zerba KE, Ferrell RE, Sing CF. Genotype-environment interaction: apolipoprotein E (ApoE) gene effects and age as an index of time and spatial context in the human. Genetics 1996; 143: 463-78.
38. Haviland MB, Lussier-Cacan S, Davignon J, Sing CF. Impact of apolipoprotein E genotype variation on means, variances, and correlations of plasma lipid, lipoprotein, and apolipoprotein traits in octogenarians. Am J Med Genet 1995; 58: 315-31.
39. Pablos-Mendez A, Mayeux R, Ngai C, Shea S, Berglund L. Association of apo E polymorphism with plasma lipid levels in a multiethnic elderly population. Arterioscler Thromb Vasc Biol 1997; 17: 3534-41.
40. Reilly SL, Ferrell RE, Sing CF. The gender-specific apolipoprotein E genotype influence on the distribution of plasma lipids and apolipoproteins in the population of Rochester, MN. III. Correlations and covariances. Am J Hum Genet 1994; 55: 1001-18.
41. Lehtimäki T, Moilanen T, Porkka K, Åkerblom HK, Rönnemaa T, Räsänen L, et al. Association between serum lipids and apolipoprotein E phenotype is influenced by diet in a population-based sample of free-living children and young adults: the Cardiovascular Risk in Young Finns Study. J Lipid Res 1995; 36: 653-61.
42. Wilson PW, Schaefer EJ, Larson MG, Ordovas JM. Apolipoprotein E alleles and risk of coronary disease. A meta-analysis. Arterioscler Thromb Vasc Biol 1996; 16: 1250-5.
43. Kuusisto J, Mykkänen L, Kervinen K, Kesäniemi YA, Laakso M. Apolipoprotein E4 phenotype is not an important risk factor for coronary heart disease or stroke in elderly subjects. Arterioscler Thromb Vasc Biol 1995; 15: 1280-6.
44. Stengard JH, Zerba KE, Pekkanen J, Ehnholm C, Nissinen A, Sing CF. Apolipoprotein E polymorphism predicts death from coronary heart disease in a longitudinal study of elderly Finnish men. Circulation 1995; 91: 265-9.
45. Hixson JE. Apolipoprotein E polymorphisms affect atherosclerosis in young males. Pathobiological Determinants of Atherosclerosis in Youth (PDAY) Research Group. Arterioscler Thromb 1991; 11: 1237-44.
46. Stengard JH, Weiss KM, Sing CF. An ecological study of association between coronary heart disease mortality rates in men and the relative frequencies of common allelic variations in the gene coding for apolipoprotein E. Hum Genet 1998; 103: 234-41.
47. Wang XL, McCredie RM, Wilcken DE. Polymorphisms of the apolipoprotein E gene and severity of coronary artery disease defined by angiography. Arterioscler Thromb Vasc Biol 1995; 15: 1030-4.
48. van Bockxmeer FM, Mamotte CD, Gibbons FR, Taylor RR. Apolipoprotein epsilon 4 homozygosity - a determinant of restenosis after coronary angioplasty. Atherosclerosis 1994; 110: 195-202.
49. Winkelmann BR, Ihnken K, Beyersdorf F, Eckel L, Skupin M, Marz W, et al. Left main coronary artery stenosis after aortic valve replacement: genetic disposition for accelerated arteriosclerosis after injury of the intact human coronary artery? Coron Artery Dis 1993; 4: 659-67.
50. McCarron MO, Delong D, Alberts MJ. APOE genotype as a risk factor for ischemic cerebrovascular disease: a meta-analysis. Neurology 1999; 53: 1308-11.
51. Lautenschlager NT, Cupples LA, Rao VS, Auerbach SA, Becker R, Burke J, et al. Risk of dementia among relatives of Alzheimer's disease patients in the MIRAGE study: what is in store for the oldest old? Neurology 1996; 46: 641-50.
52. Schellenberg GD, Boehnke M, Wijsman EM, Moore DK, Martin GM, Bird TD. Genetic association and linkage analysis of the apolipoprotein CII locus and familial Alzheimer's disease. Ann Neurol 1992; 31: 223-7.
53. Pericak-Vance MA, Bebout JL, Gaskell PC Jr, Yamaoka LH, Hung WY, Alberts MJ, et al. Linkage studies in familial Alzheimer disease: evidence for chromosome 19 linkage. Am J Hum Genet 1991; 48: 1034-50.
54. Corder EH, Saunders AM, Strittmatter WJ, Schmechel DE, Gaskell PC, Small GW, et al. Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer's disease in late onset families. Science 1993; 261: 921-3.
55. Saunders AM, Strittmatter WJ, Schmechel D, George-Hyslop PH, Pericak-Vance MA, Joo SH, et al. Association of apolipoprotein E allele epsilon 4 with late-onset familial and sporadic Alzheimer's disease. Neurology 1993; 43: 1467-72.
56. Farrer LA, Cupples LA, Haines JL, Hyman B, Kukull WA, Mayeux R, et al. 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 1997; 278: 1349-56.
57. Blacker D, Haines JL, Rodes L, Terwedow H, Go RCP, Harrell LE, et al. ApoE-4 and age at onset of Alzheimer's disease: the NIMH genetics initiative. Neurology 1997; 48: 139-47.
58. Rubinsztein DC, Easton DF. Apolipoprotein E genetic variation and Alzheimer's disease. A meta-analysis. Dement Geriatr Cogn Disord 1999; 10: 199-209.
59. Kehoe P, Wavrant-De VF, Crook R, Wu WS, Holmans P, Fenton I, et al. A full genome scan for late onset Alzheimer's disease. Hum Mol Genet 1999; 8: 237-45.
60. Bullido MJ, Artiga MJ, Recuero M, Sastre I, Garcia MA, Aldudo J, et al. A polymorphism in the regulatory region of APOE associated with risk for Alzheimer's dementia. Nat Genet 1998; 18: 69-71.
61. Lambert JC, Perez-Tur J, Dupire MJ, Galasko D, Mann D, Amouyel P, et al. Distortion of allelic expression of apolipoprotein E in Alzheimer's disease. Hum Mol Genet 1997; 6: 2151-4.
62. Artiga MJ, Bullido MJ, Frank A, Sastre I, Recuero M, Garcia MA, et al. Risk for Alzheimer's disease correlates with transcriptional activity of the APOE gene. Hum Mol Genet 1998; 7: 1887-92.
63. Lambert JC, Berr C, Pasquier F, Delacourte A, Frigard B, Cottel D, et al. Pronounced impact of Th1/E47cs mutation compared with -491 AT mutation on neural APOE gene expression and risk of developing Alzheimer's disease. Hum Mol Genet 1998; 7: 1511-6.
64. Drigalenko E, Poduslo S, Elston R. Interaction of the apolipoprotein E and CI loci in predisposing to late-onset Alzheimer's disease. Neurology 1998; 51: 131-5.
65. Hyman BT, West HL, Rebeck GW, Buldyrev SV, Mantegna RN, Ukleja M, et al. Quantitative analysis of senile plaques in Alzheimer disease: observation of log-normal size distribution and molecular epidemiology of differences associated with apolipoprotein E genotype and trisomy 21 (Down syndrome). Proc Natl Acad Sci U S A 1995; 92: 3586-90.
66. Schmechel DE, Saunders AM, Strittmatter WJ, Crain BJ, Hulette CM, Joo SH, et al. 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 1993; 90: 9649-53.
67. Johnson JK, McCleary R, Oshita MH, Cotman CW. Initiation and propagation stages of beta-amyloid are associated with distinctive apolipoprotein E, age, and gender profiles. Brain Res 1998; 798: 18-24.
68. Pirttilä T, Soininen H, Mehta PD, Heinonen O, Lehtimäki T, Bogdanovic N, et al. Apolipoprotein E genotype and amyloid load in Alzheimer disease and control brains. Neurobiol Aging 1997; 18: 121-7.
69. Poirier J, Delisle MC, Quirion R, Aubert I, Farlow M, Lahiri D, et al. Apolipoprotein E4 allele as a predictor of cholinergic deficits and treatment outcome in Alzheimer disease. Proc Natl Acad Sci U S A 1995; 92: 12260-4.
70. Arendt T, Schindler C, Bruckner MK, Eschrich K, Bigl V, Zedlick D, et al. Plastic neuronal remodeling is impaired in patients with Alzheimer's disease carrying apolipoprotein epsilon 4 allele. J Neurosci 1997; 17: 516-29.
71. Warzok RW, Kessler C, Apel G, Schwarz A, Egensperger R, Schreiber D, et al. Apolipoprotein E4 promotes incipient Alzheimer pathology in the elderly. Alzheimer Dis Assoc Disord 1998; 12: 33-9.
72. Craft S, Teri L, Edland SD, Kukull WA, Schellenberg G, McCormick WC, et al. Accelerated decline in apolipoprotein E-epsilon4 homozygotes with Alzheimer's disease. Neurology 1998; 51: 149-53.
73. Slooter AJ, Houwing-Duistermaat JJ, van Harskamp F, Cruts M, Van Broeckhoven C, Breteler MM, et al. Apolipoprotein E genotype and progression of Alzheimer's disease: the Rotterdam Study. J Neurol 1999; 246: 304-8.
74. Growdon JH, Locascio JJ, Corkin S, Gomez-Isla T, Hyman BT. Apolipoprotein E genotype does not influence rates of cognitive decline in Alzheimer's disease. Neurology 1996; 47: 444-8.
75. Strittmatter WJ, Weisgraber KH, Huang DY, Dong LM, Salvesen GS, Pericak-Vance M, et al. Binding of human apolipoprotein E to synthetic amyloid beta peptide: isoform-specific effects and implications for late-onset Alzheimer disease. Proc Natl Acad Sci U S A 1993; 90: 8098-102.
76. LaDu MJ, Falduto MT, Manelli AM, Reardon CA, Getz GS, Frail DE. Isoform-specific binding of apolipoprotein E to β-amyloid. J Biol Chem 1994; 269: 23403-6.
77. Moir RD, Atwood CS, Romano DM, Laurans MH, Huang X, Bush AI, et al. Differential effects of apolipoprotein E isoforms on metal-induced aggregation of A-beta using physiological concentrations. Biochemistry 1999; 38: 4595-603.
78. Nathan BP, Bellosta S, Sanan DA, Weisgraber KH, Mahley RW, Pitas RE. Differential effects of apo E3 and E4 on neuronal growth in vitro. Science 1994; 264: 850-2.
79. Miyata M, Smith JD. Apolipoprotein E allele-specific antioxidant activity and specific effects on cytotoxicity by oxidative insults and β-amyloid peptides. Nat Genet 1996; 14: 55-61.
80. Bales KR, Verina T, Dodel RC, Du Y, Altstiel L, Bender M, et al. Lack of apolipoprotein E dramatically reduces amyloid beta-peptide deposition. Nat Genet 1997; 17: 263-4.
81. Holtzman DM, Bales KR, Wu S, Bhat P, Parsadanian M, Fagan AM, et al. Expression of human apolipoprotein E reduces amyloid-beta deposition in a mouse model of Alzheimer's disease. J Clin Invest 1999; 103: R15-21.
82. Zarow C, Zaias B, Lyness SA, Chui H. Cerebral amyloid angiopathy in Alzheimer disease is associated with apolipoprotein E4 and cortical neuron loss. Alzheimer Dis Assoc Disord 1999; 13: 1-8.
83. Premkumar DR, Cohen DL, Hedera P, Friedland RP, Kalaria RN. Apolipoprotein E-epsilon4 alleles in cerebral amyloid angiopathy and cerebrovascular pathology associated with Alzheimer's disease. Am J Pathol 1996; 148: 2083-95.
84. Greenberg SM, Rebeck GW, Vonsattel JP, Gomez-Isla T, Hyman BT. Apolipoprotein E epsilon 4 and cerebral hemorrhage associated with amyloid angiopathy. Ann Neurol 1995; 38: 254-9.
85. Greenberg SM, Vonsattel JP, Segal AZ, Chiu RI, Clatworthy AE, Liao A, et al. Association of apolipoprotein E epsilon2 and vasculopathy in cerebral amyloid angiopathy. Neurology 1998; 50: 961-5.
86. Nicoll JA, Burnett C, Love S, Graham DI, Dewar D, Ironside JW, et al. High frequency of apolipoprotein E epsilon 2 allele in hemorrhage due to cerebral amyloid angiopathy. Ann Neurol 1997; 41: 716-21.
87. Mann DM, Brown SM, Owen F, Baba M, Iwatsubo T. Amyloid beta protein (A beta) deposition in dementia with Lewy bodies: predominance of A beta 42(43) and paucity of A beta 40 compared with sporadic Alzheimer's disease. Neuropathol Appl Neurobiol 1998; 24: 187-94.
88. St Clair D, Norrman J, Perry R, Yates C, Wilcock G, Brookes A. Apolipoprotein E epsilon 4 allele frequency in patients with Lewy body dementia, Alzheimer's disease and age-matched controls. Neurosci Lett 1994; 176: 45-6.
89. Hardy J, Crook R, Prihar G, Roberts G, Raghavan R, Perry R. Senile dementia of the Lewy body type has an apolipoprotein E epsilon 4 allele frequency intermediate between controls and Alzheimer's disease. Neurosci Lett 1994; 182: 1-2.
90. Del BR, Comi GP, Bresolin N, Castelli E, Conti E, Degiuli A, et al. The apolipoprotein E epsilon4 allele causes a faster decline of cognitive performances in Down's syndrome subjects. J Neurol Sci 1997; 145: 87-91.
91. Prasher VP, Chowdhury TA, Rowe BR, Bain SC. ApoE genotype and Alzheimer's disease in adults with Down syndrome: meta-analysis. Am J Ment Retard 1997; 102: 103-10.
92. Lai F, Kammann E, Rebeck GW, Anderson A, Chen Y, Nixon RA. APOE genotype and gender effects on Alzheimer disease in 100 adults with Down syndrome. Neurology 1999; 53: 331-6.
93. Rubinsztein DC, Hon J, Stevens F, Pyrah I, Tysoe C, Huppert FA, et al. Apo E genotypes and risk of dementia in Down syndrome. Am J Med Genet 1999; 88: 344-7.
94. Koller WC, Glatt SL, Hubble JP, Paolo A, Troster AI, Handler MS, et al. Apolipoprotein E genotypes in Parkinson's disease with and without dementia. Ann Neurol 1995; 37: 242-5.
95. Tabaton M, Rolleri M, Masturzo P, Cammarata S, Angelini G, Hansen LA, et al. Apolipoprotein E epsilon 4 allele frequency is not increased in progressive supranuclear palsy. Neurology 1995; 45: 1764-5.
96. Mui S, Rebeck GW, McKenna-Yasek D, Hyman BT, Brown RJ. Apolipoprotein E epsilon 4 allele is not associated with earlier age at onset in amyotrophic lateral sclerosis. Ann Neurol 1995; 38: 460-3.
97. Evangelou N, Jackson M, Beeson D, Palace J. Association of the APOE epsilon4 allele with disease activity in multiple sclerosis. J Neurol Neurosurg Psychiatry 1999; 67: 203-5.
98. Blumcke I, Brockhaus A, Scheiwe C, Rollbrocker B, Wolf HK, Elger CE, et al. The apolipoprotein E epsilon 4 allele is not associated with early onset temporal lobe epilepsy. Neuroreport 1997; 8: 1235-7.
99. Kehoe P, Krawczak M, Harper PS, Owen MJ, Jones AL. Age of onset in Huntington disease: sex specific influence of apolipoprotein E genotype and normal CAG repeat length. J Med Genet 1999; 36: 108-11.
100. Papassotiropoulos A, Bagli M, Jessen F, Rao ML, Schwab SG, Heun R. Early-onset and late-onset depression are independent of the genetic polymorphism of apolipoprotein E. Dement Geriatr Cogn Disord 1999; 10: 258-61.
101. Saunders AM, Schmader K, Breitner JC, Benson MD, Brown WT, Goldfarb L, et al. Apolipoprotein epsilon4 allele distributions in late-onset Alzheimer's diseases and in other amyloid-forming diseases. Lancet 1993; 710-1.
102. Zerr I, Helmhold M, Poser S, Armstrong VW, Weber T. Apolipoprotein E phenotype frequency and cerebrospinal fluid concentration are not associated with Creutzfeldt-Jakob disease. Arch Neurol 1996; 53: 1233-8.
103. Dunlop O, Goplen AK, Liestol K, Myrvang B, Rootwelt H, Christophersen B, et al. HIV dementia and apolipoprotein E. Acta Neurol Scand 1997; 95: 315-8.
104. Feskens EJ, Havekes LM, Kalmijn S, de Kniff P, Launer LJ, Kromhout D. Apolipoprotein e4 allele and cognitive decline in elderly men. BMJ 1994; 309: 1202-6.
105. Yaffe K, Cauley J, Sands L, Browner W. Apolipoprotein E phenotype and cognitive decline in a prospective study of elderly community women. Arch Neurol 1997; 54: 1110-4.
106. Jonker C, Schmand B, Lindeboom J, Havekes LM, Launer LJ. Association between apolipoprotein E epsilon4 and the rate of cognitive decline in community-dwelling elderly individuals with and without dementia. Arch Neurol 1998; 55: 1065-9.
107. Slooter AJ, van Duijn CM, Bots ML, Ott A, Breteler MB, De Voecht J, et al. Apolipoprotein E genotype, atherosclerosis, and cognitive decline: the Rotterdam Study. J Neural Transm Suppl 1998; 53: 17-29.
108. Carmelli D, Swan GE, Reed T, Miller B, Wolf PA, Jarvik GP, et al. Midlife cardiovascular risk factors, ApoE, and cognitive decline in elderly male twins. Neurology 1998; 50: 1580-5.
109. Haan MN, Shemanski L, Jagust WJ, Manolio TA, Kuller L. The role of APOE epsilon4 in modulating effects of other risk factors for cognitive decline in elderly persons. JAMA 1999; 282: 40-6.
110. Small BJ, Basun H, Backman L. Three-year changes in cognitive performance as a function of apolipoprotein E genotype: evidence from very old adults without dementia. Psychol Aging 1998; 13: 80-7.
111. Mortimer JA, van Duijn CM, Chandra V, Fratiglioni L, Graves AB, Heyman A, et al. Head trauma as a risk factor for Alzheimer's disease: a collaborative re-analysis of case-control studies. EURODEM Risk Factors Research Group. Int J Epidemiol 1991; 20 Suppl 2: S28-35.
112. Nemetz PN, Leibson C, Naessens JM, Beard M, Kokmen E, Annegers JF, et al. Traumatic brain injury and time to onset of Alzheimer's disease: a population-based study. Am J Epidemiol 1999; 149: 32-40.
113. Tokuda T, Ikeda S, Yanagisawa N, Ihara Y, Glenner GG. Re-examination of ex-boxers' brains using immunohistochemistry with antibodies to amyloid beta-protein and tau protein. Acta Neuropathol (Berl) 1991; 82: 280-5.
114. Nicoll JA, Roberts GW, Graham DI. Apolipoprotein E epsilon 4 allele is associated with deposition of amyloid beta-protein following head injury. Nat Med 1995; 1: 135-7.
115. Mayeux R, Ottman R, Maestre G, Ngai C, Tang MX, Ginsberg H, et al. Synergistic effects of traumatic head injury and apolipoprotein-epsilon 4 in patients with Alzheimer's disease. Neurology 1995; 45: 555-7.
116. Jordan BD, Relkin NR, Ravdin LD, Jacobs AR, Bennett A, Gandy S. Apolipoprotein E epsilon4 associated with chronic traumatic brain injury in boxing. JAMA 1997; 278: 136-40.
117. Teasdale GM, Nicoll JA, Murray G, Fiddes M. Association of apolipoprotein E polymorphism with outcome after head injury. Lancet 1997; 350: 1069-71.
118. Friedman G, Froom P, Sazbon L, Grinblatt I, Shochina M, Tsenter J, et al. Apolipoprotein E-epsilon4 genotype predicts a poor outcome in survivors of traumatic brain injury. Neurology 1999; 52: 244-8.
119. Tardiff BE, Newman MF, Saunders AM, Strittmatter WJ, Blumenthal JA, White WD, et al. Preliminary report of a genetic basis for cognitive decline after cardiac operations. The Neurologic Outcome Research Group of the Duke Heart Center. Ann Thorac Surg 1997; 64: 715-20.
120. Kelly JP. Traumatic brain injury and concussion in sports. JAMA 1999; 282: 989-91.
121. Caulfield TA. The law, adolescents, and the APOE epsilon 4 genotype: a view from Canada. Genet Test 1999; 3: 107-13.
122. Bertomeu A, Ros E, Zambon D, Vela M, Perez-Ayuso RM, Targarona E, et al. Apolipoprotein E polymorphism and gallstones. Gastroenterology 1996; 111: 1603-10.
123. Niemi M, Kervinen K, Rantala A, Kauma H, Päivänsalo M, Savolainen MJ, et al. The role of apolipoprotein E and glucose intolerance in gallstone disease in middle aged subjects. Gut 1999; 44: 557-62.
124. Portincasa P, van Erpecum KJ, van De Meeberg PC, Dallinga-Thie GM, de Bruin IW, van Berge-Henegouwen GP. Apolipoprotein E4 genotype and gallbladder motility influence speed of gallstone clearance and risk of recurrence after extracorporeal shock-wave lithotripsy. Hepatology 1996; 24: 580-7.
125. Juvonen T, Kervinen K, Kairaluoma MI, Lajunen LH, Kesäniemi YA. Gallstone cholesterol content is related to apolipoprotein E polymorphism. Gastroenterology 1993; 104: 1806-13.
126. Miettinen TA, Gylling H, Vanhanen H, Ollus A. Cholesterol absorption, elimination, and synthesis related to LDL kinetics during varying fat intake in men with different apoprotein E phenotypes. Arterioscler Thromb 1992; 12: 1044-52.
127. Cauley JA, Zmuda JM, Yaffe K, Kuller LH, Ferrell RE, Wisniewski SR, et al. Apolipoprotein E polymorphism: a new genetic marker of hip fracture risk-The Study of Osteoporotic Fractures. J Bone Miner Res 1999; 14: 1175-81.
128. Itzhaki RF, Lin WR, Shang D, Wilcock GK, Faragher B, Jamieson GA. Herpes simplex virus type 1 in brain and risk of Alzheimer's disease. Lancet 1997; 349: 241-4.
129. Lin WR, Tullo AB, Itzhaki RF. Apolipoprotein E and herpes virus diseases: herpes simplex keratitis. Eur J Hum Genet 1999; 7: 401-3.
130. Freitas EM, Zhang WJ, Lalonde JP, Tay GK, Gaudieri S, Ashworth LK, et al. Sequencing of 42kb of the APO E-C2 gene cluster reveals a new gene: PEREC1. DNA Seq 1998; 9: 89-100.
131. Jahn CE, Oette K, Esser A, von Bergmann K, Leiss O. Increased prevalence of apolipoprotein E2 in patients with retinitis pigmentosa. Ophthalmic Res 1987; 19: 285-8.
132. Huq L, McLachlan T, Hammer HM, Bedford D, Packard CJ, Shepherd J, et al. An increased incidence of apolipoprotein E2/E2 and E4/E4 in retinitis pigmentosa. Lipids 1993; 28: 995-8.
133. Romas SN, Tang MX, Berglund L, Mayeux R. APOE genotype, plasma lipids, lipoproteins, and AD in community elderly. Neurology 1999; 53: 517-21.
134. Slooter AJ, Cruts M, Ott A, Bots ML, Witteman JC, Hofman A, et al. The effect of APOE on dementia is not through atherosclerosis: the Rotterdam Study. Neurology 1999; 53: 1593-5.
135. Post SG, Whitehouse PJ, Binstock RH, Bird TD, Eckert SK, Farrer LA, et al. The clinical introduction of genetic testing for Alzheimer disease. An ethical perspective. JAMA 1997; 277: 832-6.