The forgotten APOE allele: A review of the evidence and suggested mechanisms for the protective effect of APOE e2

Neuroscience and Biobehavioral Reviews

Volumn 37, Issue 10, 2013, Pages 2878-2886

  Suri, Sana ^a   Heise, Verena ^a   Trachtenberg, Aaron J ^a   Mackay, Clare E ^a  

^a UNIVERSITY OF OXFORD   (United Kingdom)

Author keywords

Alzheimer's disease; APOE e2; Cognitive health; Longevity; Neuroprotection

Indexed keywords

AMYLOID BETA PROTEIN; APOLIPOPROTEIN E; APOLIPOPROTEIN E2; APOLIPOPROTEIN E3; APOLIPOPROTEIN E4;

AGING; ALZHEIMER DISEASE; ANTIINFLAMMATORY ACTIVITY; ANTIOXIDANT ACTIVITY; BRAIN FUNCTION; BRAIN REGION; COGNITION; DIFFUSION TENSOR IMAGING; ENTORHINAL CORTEX; ETHNICITY; FUNCTIONAL MAGNETIC RESONANCE IMAGING; GENE FREQUENCY; GENOTYPE; HIPPOCAMPUS; HUMAN; LONGEVITY; NERVE CELL PLASTICITY; NEUROPATHOLOGY; NEUROPROTECTION; OXIDATIVE STRESS; PRIORITY JOURNAL; PROTEIN DEGRADATION; PROTEIN FUNCTION; PROTEIN STRUCTURE; QUALITY OF LIFE; REVIEW; RISK FACTOR; SENILE PLAQUE;

ALZHEIMER'S DISEASE; APOE E2; COGNITIVE HEALTH; LONGEVITY; NEUROPROTECTION;

ALLELES; APOLIPOPROTEIN E2; COGNITION DISORDERS; GENOTYPE; HUMANS; LONGEVITY; NEURODEGENERATIVE DISEASES; RISK FACTORS;

EID: 84889653145     PISSN: 01497634     EISSN: 18737528     Source Type: Journal    
DOI: 10.1016/j.neubiorev.2013.10.010     Document Type: Review

References (124)

1. Aleshkov S., Abraham C.R., Zannis V.I. Interaction of nascent ApoE2, ApoE3, and ApoE4 isoforms expressed in mammalian cells with amyloid peptide beta (1-40). Relevance to Alzheimer's disease. Biochemistry 1997, 36:10571-10580.
2. Alexopoulos P., Richter-Schmidinger T., Horn M., Maus S., Reichel M., Sidiropoulos C., Rhein C., Lewczuk P., Doerfler A., Kornhuber J. Hippocampal volume differences between healthy young apolipoprotein E epsilon2 and epsilon4 carriers. Journal of Alzheimer's Disease: JAD 2011, 26:207-210.
3. Bales K.R., Dodart J.C., DeMattos R.B., Holtzman D.M., Paul S.M. Apolipoprotein E, amyloid, and Alzheimer disease. Molecular Interventions 2002, 2:363-375. 339.
4. Beaulieu C. The basis of anisotropic water diffusion in the nervous system - a technical review. NMR in Biomedicine 2002, 15:435-455.
5. Benzi G., Moretti A. Are reactive oxygen species involved in Alzheimer's disease?. Neurobiology of Aging 1995, 16:661-674.
6. Berlau D.J., Corrada M.M., Head E., Kawas C.H. APOE epsilon2 is associated with intact cognition but increased Alzheimer pathology in the oldest old. Neurology 2009, 72:829-834.
7. Bernardi L., Maletta R.G., Tomaino C., Smirne N., Di Natale M., Perri M., Longo T., Colao R., Curcio S.A., Puccio G., Mirabelli M., Kawarai T., Rogaeva E., St George Hyslop P.H., Passarino G., De Benedictis G., Bruni A.C. The effects of APOE and tau gene variability on risk of frontotemporal dementia. Neurobiology of Aging 2006, 27:702-709.
8. Biffi A., Anderson C.D., Jagiella J.M., Schmidt H., Kissela B., Hansen B.M., Jimenez-Conde J., Pires C.R., Ayres A.M., Schwab K., Cortellini L., Pera J., Urbanik A., Romero J.M., Rost N.S., Goldstein J.N., Viswanathan A., Pichler A., Enzinger C., Rabionet R., Norrving B., Tirschwell D.L., Selim M., Brown D.L., Silliman S.L., Worrall B.B., Meschia J.F., Kidwell C.S., Broderick J.P., Greenberg S.M., Roquer J., Lindgren A., Slowik A., Schmidt R., Woo D., Rosand J. APOE genotype and extent of bleeding and outcome in lobar intracerebral haemorrhage: a genetic association study. Lancet Neurology 2011, 10:702-709.
9. Blanche H., Cabanne L., Sahbatou M., Thomas G. A study of French centenarians: are ACE and APOE associated with longevity?. Comptes rendus de l'Academie des sciences. Serie III, Sciences de la vie 2001, 324:129-135.
10. Bliss T.V., Collingridge G.L. A synaptic model of memory: long-term potentiation in the hippocampus. Nature 1993, 361:31-39.
11. Braak H., Braak E. Neuropathological stageing of Alzheimer-related changes. Acta Neuropathologica 1991, 82:239-259.
12. Bunce D., Anstey K.J., Cherbuin N., Gautam P., Sachdev P., Easteal S. APOE genotype and entorhinal cortex volume in non-demented community-dwelling adults in midlife and early old age. Journal of Alzheimer's Disease: JAD 2012, 30:935-942.
13. Burt T.D., Agan B.K., Marconi V.C., He W., Kulkarni H., Mold J.E., Cavrois M., Huang Y., Mahley R.W., Dolan M.J., McCune J.M., Ahuja S.K. Apolipoprotein (apo) E4 enhances HIV-1 cell entry in vitro, and the APOE epsilon4/epsilon4 genotype accelerates HIV disease progression. Proceedings of the National Academy of Sciences of the United States of America 2008, 105:8718-8723.
14. Caselli R.J., Dueck A.C., Osborne D., Sabbagh M.N., Connor D.J., Ahern G.L., Baxter L.C., Rapcsak S.Z., Shi J., Woodruff B.K., Locke D.E., Snyder C.H., Alexander G.E., Rademakers R., Reiman E.M. Longitudinal modeling of age-related memory decline and the APOE epsilon4 effect. The New England Journal of Medicine 2009, 361:255-263.
15. Cauley J.A., Eichner J.E., Kamboh M.I., Ferrell R.E., Kuller L.H. Apo E allele frequencies in younger (age 42-50) vs older (age 65-90) women. Genetic Epidemiology 1993, 10:27-34.
16. Chiang G.C., Insel P.S., Tosun D., Schuff N., Truran-Sacrey D., Raptentsetsang S.T., Jack C.R., Aisen P.S., Petersen R.C., Weiner M.W. Hippocampal atrophy rates and CSF biomarkers in elderly APOE2 normal subjects. Neurology 2010, 75:1976-1981.
17. Chiang G.C., Zhan W., Schuff N., Weiner M.W. White matter alterations in cognitively normal apoE epsilon2 carriers: insight into Alzheimer resistance?. AJNR. American Journal of Neuroradiology 2012, 33:1392-1397.
18. Corder E.H., Lannfelt L., Viitanen M., Corder L.S., Manton K.G., Winblad B., Basun H. Apolipoprotein E genotype determines survival in the oldest old (85 years or older) who have good cognition. Archives of Neurology 1996, 53:418-422.
19. Corder E.H., Saunders A.M., Risch N.J., Strittmatter W.J., Schmechel D.E., Gaskell P.C., Rimmler J.B., Locke P.A., Conneally P.M., Schmader K.E., et al. Protective effect of apolipoprotein E type 2 allele for late onset Alzheimer disease. Nature Genetics 1994, 7:180-184.
20. Corder E.H., Saunders A.M., Strittmatter W.J., Schmechel D.E., Gaskell P.C., Small G.W., Roses A.D., Haines J.L., Pericak-Vance M.A. Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer's disease in late onset families. Science (New York, N. Y.) 1993, 261:921-923.
21. de Toledo-Morrell L., Goncharova I., Dickerson B., Wilson R.S., Bennett D.A. From healthy aging to early Alzheimer's disease: in vivo detection of entorhinal cortex atrophy. Annals of the New York Academy of Sciences 2000, 911:240-253.
22. DeKosky S.T., Scheff S.W. Synapse loss in frontal cortex biopsies in Alzheimer's disease: correlation with cognitive severity. Annals of Neurology 1990, 27:457-464.
23. DeMattos R.B., Bales K.R., Cummins D.J., Dodart J.C., Paul S.M., Holtzman D.M. Peripheral anti-A beta antibody alters CNS and plasma A beta clearance and decreases brain A beta burden in a mouse model of Alzheimer's disease. Proceedings of the National Academy of Sciences of the United States of America 2001, 98:8850-8855.
24. den Heijer T., Oudkerk M., Launer L.J., van Duijn C.M., Hofman A., Breteler M.M. Hippocampal, amygdalar, and global brain atrophy in different apolipoprotein E genotypes. Neurology 2002, 59:746-748.
25. Dickerson B.C., Goncharova I., Sullivan M.P., Forchetti C., Wilson R.S., Bennett D.A., Beckett L.A., deToledo-Morrell L. MRI-derived entorhinal and hippocampal atrophy in incipient and very mild Alzheimer's disease. Neurobiology of Aging 2001, 22:747-754.
26. Drenos F., Kirkwood T.B. Selection on alleles affecting human longevity and late-life disease: the example of apolipoprotein E. PLoS One 2010, 5:e10022.
27. Drouet B., Fifre A., Pincon-Raymond M., Vandekerckhove J., Rosseneu M., Gueant J.L., Chambaz J., Pillot T. ApoE protects cortical neurones against neurotoxicity induced by the non-fibrillar C-terminal domain of the amyloid-beta peptide. Journal of Neurochemistry 2001, 76:117-127.
28. Dumanis S.B., Tesoriero J.A., Babus L.W., Nguyen M.T., Trotter J.H., Ladu M.J., Weeber E.J., Turner R.S., Xu B., Rebeck G.W., Hoe H.S. ApoE4 decreases spine density and dendritic complexity in cortical neurons in vivo. The Journal of Neuroscience: The Official Journal of the Society for Neuroscience 2009, 29:15317-15322.
29. Fagan A.M., Holtzman D.M. Astrocyte lipoproteins, effects of apoE on neuronal function, and role of apoE in amyloid-beta deposition in vivo. Microscopy Research and Technique 2000, 50:297-304.
30. Fagan A.M., Watson M., Parsadanian M., Bales K.R., Paul S.M., Holtzman D.M. Human and murine ApoE markedly alters A beta metabolism before and after plaque formation in a mouse model of Alzheimer's disease. Neurobiology of Disease 2002, 9:305-318.
31. Fan M., Liu B., Zhou Y., Zhen X., Xu C., Jiang T. Cortical thickness is associated with different apolipoprotein E genotypes in healthy elderly adults. Neuroscience Letters 2010, 479:332-336.
32. Farrer L.A., Cupples L.A., Haines J.L., Hyman B., Kukull W.A., Mayeux R., Myers R.H., Pericak-Vance M.A., Risch N., van Duijn C.M. 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: The Journal of the American Medical Association 1997, 278:1349-1356.
33. Fennema-Notestine C., Panizzon M.S., Thompson W.R., Chen C.H., Eyler L.T., Fischl B., Franz C.E., Grant M.D., Jak A.J., Jernigan T.L., Lyons M.J., Neale M.C., Seidman L.J., Tsuang M.T., Xian H., Dale A.M., Kremen W.S. Presence of ApoE epsilon4 allele associated with thinner frontal cortex in middle age. Journal of Alzheimer's Disease: JAD 2011, 26(Suppl. 3):49-60.
34. Filippini N., Ebmeier K.P., MacIntosh B.J., Trachtenberg A.J., Frisoni G.B., Wilcock G.K., Beckmann C.F., Smith S.M., Matthews P.M., Mackay C.E. Differential effects of the APOE genotype on brain function across the lifespan. NeuroImage 2011, 54:602-610.
35. Filippini N., MacIntosh B.J., Hough M.G., Goodwin G.M., Frisoni G.B., Smith S.M., Matthews P.M., Beckmann C.F., Mackay C.E. Distinct patterns of brain activity in young carriers of the APOE-epsilon4 allele. Proceedings of the National Academy of Sciences of the United States of America 2009, 106:7209-7214.
36. Frisoni G.B., Louhija J., Geroldi C., Trabucchi M. Longevity and the epsilon2 allele of apolipoprotein E: the Finnish Centenarians Study. The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences 2001, 56:M75-M78.
37. Fullerton S.M., Clark A.G., Weiss K.M., Nickerson D.A., Taylor S.L., Stengard J.H., Salomaa V., Vartiainen E., Perola M., Boerwinkle E., Sing C.F. Apolipoprotein E variation at the sequence haplotype level: implications for the origin and maintenance of a major human polymorphism. American Journal of Human Genetics 2000, 67:881-900.
38. Ghebremedhin E., Schultz C., Botez G., Rub U., Sassin I., Braak E., Braak H. Argyrophilic grain disease is associated with apolipoprotein E epsilon 2 allele. Acta Neuropathologica 1998, 96:222-224.
39. Greenberg S.M. Cerebral amyloid angiopathy: prospects for clinical diagnosis and treatment. Neurology 1998, 51:690-694.
40. Greenberg S.M., Vonsattel J.P., Segal A.Z., Chiu R.I., Clatworthy A.E., Liao A., Hyman B.T., Rebeck G.W. Association of apolipoprotein E epsilon2 and vasculopathy in cerebral amyloid angiopathy. Neurology 1998, 50:961-965.
41. Griffin W.S., Sheng J.G., Royston M.C., Gentleman S.M., McKenzie J.E., Graham D.I., Roberts G.W., Mrak R.E. Glial-neuronal interactions in Alzheimer's disease: the potential role of a 'cytokine cycle' in disease progression. Brain Pathology (Zurich, Switzerland) 1998, 8:65-72.
42. Haan M.N., Shemanski L., Jagust W.J., Manolio T.A., Kuller L. The role of APOE epsilon4 in modulating effects of other risk factors for cognitive decline in elderly persons. JAMA: The Journal of the American Medical Association 1999, 282:40-46.
43. Hamilton W.D. The moulding of senescence by natural selection. Journal of Theoretical Biology 1966, 12:12-45.
44. Hanlon C.S., Rubinsztein D.C. Arginine residues at codons 112 and 158 in the apolipoprotein E gene correspond to the ancestral state in humans. Atherosclerosis 1995, 112:85-90.
45. Hardy J., Selkoe D.J. The amyloid hypothesis of Alzheimer's disease: progress and problems on the road to therapeutics. Science (New York, N. Y.) 2002, 297:353-356.
46. Hatters D.M., Peters-Libeu C.A., Weisgraber K.H. Apolipoprotein E structure: insights into function. Trends in Biochemical Sciences 2006, 31:445-454.
47. Heise V., Filippini N., Ebmeier K.P., Mackay C.E. The APOE varepsilon4 allele modulates brain white matter integrity in healthy adults. Molecular Psychiatry 2011, 16:908-916.
48. Helkala E.L., Koivisto K., Hanninen T., Vanhanen M., Kervinen K., Kuusisto J., Mykkanen L., Kesaniemi Y.A., Laakso M., Riekkinen P. The association of apolipoprotein E polymorphism with memory: a population based study. Neuroscience Letters 1995, 191:141-144.
49. Helkala E.L., Koivisto K., Hanninen T., Vanhanen M., Kervinen K., Kuusisto J., Mykkanen L., Kesaniemi Y.A., Laakso M., Riekkinen P. Memory functions in human subjects with different apolipoprotein E phenotypes during a 3-year population-based follow-up study. Neuroscience Letters 1996, 204:177-180.
50. Henderson A.S., Easteal S., Jorm A.F., Mackinnon A.J., Korten A.E., Christensen H., Croft L., Jacomb P.A. Apolipoprotein E allele epsilon 4, dementia, and cognitive decline in a population sample. Lancet 1995, 346:1387-1390.
51. Herrup K. Reimagining Alzheimer's disease - an age-based hypothesis. The Journal of Neuroscience: The Official Journal of the Society for Neuroscience 2010, 30:16755-16762.
52. Hixson J.E., Cox L.A., Borenstein S. The baboon apolipoprotein E gene: structure, expression, and linkage with the gene for apolipoprotein C-1. Genomics 1988, 2:315-323.
53. Holtzman D.M. Role of apoe/Abeta interactions in the pathogenesis of Alzheimer's disease and cerebral amyloid angiopathy. Journal of Molecular Neuroscience: MN 2001, 17:147-155.
54. Holtzman D.M. In vivo effects of ApoE and clusterin on amyloid-ß metabolism and neuropathology. Journal of Molecular Neuroscience 2004, 23:247-254.
55. Huang Y. Roles of apolipoprotein E4 (ApoE4) in the pathogenesis of Alzheimer's disease: lessons from ApoE mouse modelsBiochemical Society. Transactions 2011, 39:924-932.
56. Hyman B.T., Gomez-Isla T., Briggs M., Chung H., Nichols S., Kohout F., Wallace R. Apolipoprotein E and cognitive change in an elderly population. Annals of Neurology 1996, 40:55-66.
57. Jack C.R., Barkhof F., Bernstein M.A., Cantillon M., Cole P.E., Decarli C., Dubois B., Duchesne S., Fox N.C., Frisoni G.B., Hampel H., Hill D.L., Johnson K., Mangin J.F., Scheltens P., Schwarz A.J., Sperling R., Suhy J., Thompson P.M., Weiner M., Foster N.L. Steps to standardization and validation of hippocampal volumetry as a biomarker in clinical trials and diagnostic criterion for Alzheimer's disease. Alzheimer's & Dementia: The Journal of the Alzheimer's Association 2011, 7:474-485. e474.
58. Jiang Q., Lee C.Y., Mandrekar S., Wilkinson B., Cramer P., Zelcer N., Mann K., Lamb B., Willson T.M., Collins J.L., Richardson J.C., Smith J.D., Comery T.A., Riddell D., Holtzman D.M., Tontonoz P., Landreth G.E. ApoE promotes the proteolytic degradation of Abeta. Neuron 2008, 58:681-693.
59. Jordan J., Galindo M.F., Miller R.J., Reardon C.A., Getz G.S., LaDu M.J. Isoform-specific effect of apolipoprotein E on cell survival and beta-amyloid-induced toxicity in rat hippocampal pyramidal neuronal cultures. The Journal of Neuroscience: The Official Journal of the Society for Neuroscience 1998, 18:195-204.
60. LaDu M.J., Falduto M.T., Manelli A.M., Reardon C.A., Getz G.S., Frail D.E. Isoform-specific binding of apolipoprotein E to beta-amyloid. The Journal of Biological Chemistry 1994, 269:23403-23406.
61. Lanz T.A., Carter D.B., Merchant K.M. Dendritic spine loss in the hippocampus of young PDAPP and Tg2576 mice and its prevention by the ApoE2 genotype. Neurobiology of Disease 2003, 13:246-253.
62. Lewis S.J., Brunner E.J. Methodological problems in genetic association studies of longevity - the apolipoprotein E gene as an example. International Journal of Epidemiology 2004, 33:962-970.
63. Lippa C.F., Smith T.W., Saunders A.M., Hulette C., Pulaski-Salo D., Roses A.D. Apolipoprotein E-epsilon 2 and Alzheimer's disease: genotype influences pathologic phenotype. Neurology 1997, 48:515-519.
64. Liu Y., Paajanen T., Westman E., Zhang Y., Wahlund L.O., Simmons A., Tunnard C., Sobow T., Proitsi P., Powell J., Mecocci P., Tsolaki M., Vellas B., Muehlboeck S., Evans A., Spenger C., Lovestone S., Soininen H. APOE epsilon2 allele is associated with larger regional cortical thicknesses and volumes. Dementia and Geriatric Cognitive Disorders 2010, 30:229-237.
65. Louhija J., Miettinen H.E., Kontula K., Tikkanen M.J., Miettinen T.A., Tilvis R.S. Aging and genetic variation of plasma apolipoproteins. Relative loss of the apolipoprotein E4 phenotype in centenarians. Arteriosclerosis and Thrombosis: A Journal of Vascular Biology/American Heart Association 1994, 14:1084-1089.
66. Love S., Siew L.K., Dawbarn D., Wilcock G.K., Ben-Shlomo Y., Allen S.J. Premorbid effects of APOE on synaptic proteins in human temporal neocortex. Neurobiology of Aging 2006, 27:797-803.
67. Ma J., Yee A., Brewer H.B., Das S., Potter H. Amyloid-associated proteins alpha 1-antichymotrypsin and apolipoprotein E promote assembly of Alzheimer beta-protein into filaments. Nature 1994, 372:92-94.
68. Mahley R.W. Apolipoprotein E: cholesterol transport protein with expanding role in cell biology. Science (New York, N. Y.) 1988, 240:622-630.
69. Mahley R.W., Huang Y. Apolipoprotein e sets the stage: response to injury triggers neuropathology. Neuron 2012, 76:871-885.
70. Mahley R.W., Huang Y. Small-molecule structure correctors target abnormal protein structure and function: structure corrector rescue of apolipoprotein E4-associated neuropathology. Journal of Medicinal Chemistry 2012, 55:8997-9008.
71. Mahley R.W., Rall S.C. Is epsilon4 the ancestral human apoE allele?. Neurobiology of Aging 1999, 20:429-430.
72. Mahley R.W., Weisgraber K.H., Huang Y. Apolipoprotein E4: a causative factor and therapeutic target in neuropathology, including Alzheimer's disease. Proceedings of the National Academy of Sciences of the United States of America 2006, 103:5644-5651.
73. Mahley R.W., Weisgraber K.H., Huang Y. Apolipoprotein E: structure determines function, from atherosclerosis to Alzheimer's disease to AIDS. Journal of Lipid Research 2009, 50(Suppl.):S183-S188.
74. Masliah E., Terry R.D., DeTeresa R.M., Hansen L.A. Immunohistochemical quantification of the synapse-related protein synaptophysin in Alzheimer disease. Neuroscience Letters 1989, 103:234-239.
75. Mayeux R., Small S.A., Tang M., Tycko B., Stern Y. Memory performance in healthy elderly without Alzheimer's disease: effects of time and apolipoprotein-E. Neurobiology of Aging 2001, 22:683-689.
76. McCarron M.O., Nicoll J.A. Apolipoprotein E genotype and cerebral amyloid angiopathy-related hemorrhage. Annals of the New York Academy of Sciences 2000, 903:176-179.
77. McCarron M.O., Nicoll J.A., Stewart J., Ironside J.W., Mann D.M., Love S., Graham D.I., Dewar D. The apolipoprotein E epsilon2 allele and the pathological features in cerebral amyloid angiopathy-related hemorrhage. Journal of Neuropathology and Experimental Neurology 1999, 58:711-718.
78. Miyata M., Smith J.D. Apolipoprotein E allele-specific antioxidant activity and effects on cytotoxicity by oxidative insults and beta-amyloid peptides. Nature Genetics 1996, 14:55-61.
79. Mondadori C.R., de Quervain D.J., Buchmann A., Mustovic H., Wollmer M.A., Schmidt C.F., Boesiger P., Hock C., Nitsch R.M., Papassotiropoulos A., Henke K. Better memory and neural efficiency in young apolipoprotein E epsilon4 carriers. Cerebral Cortex (New York, N. Y.: 1991) 2007, 17:1934-1947.
80. Morris C.M., Benjamin R., Leake A., McArthur F.K., Candy J.M., Ince P.G., Torvik A., Bjertness E., Edwardson J.A. Effect of apolipoprotein E genotype on Alzheimer's disease neuropathology in a cohort of elderly Norwegians. Neuroscience Letters 1995, 201:45-47.
81. Morrow J.A., Segall M.L., Lund-Katz S., Phillips M.C., Knapp M., Rupp B., Weisgraber K.H. Differences in stability among the human apolipoprotein E isoforms determined by the amino-terminal domain. Biochemistry 2000, 39:11657-11666.
82. Mrak R.E., Griffin W.S. Glia and their cytokines in progression of neurodegeneration. Neurobiology of Aging 2005, 26:349-354.
83. Myers R.H., Schaefer E.J., Wilson P.W., D'Agostino R., Ordovas J.M., Espino A., Au R., White R.F., Knoefel J.E., Cobb J.L., McNulty K.A., Beiser A., Wolf P.A. Apolipoprotein E epsilon4 association with dementia in a population-based study: the Framingham study. Neurology 1996, 46:673-677.
84. Nagy Z., Esiri M.M., Jobst K.A., Johnston C., Litchfield S., Sim E., Smith A.D. Influence of the apolipoprotein E genotype on amyloid deposition and neurofibrillary tangle formation in Alzheimer's disease. Neuroscience 1995, 69:757-761.
85. Nathan B.P., Bellosta S., Sanan D.A., Weisgraber K.H., Mahley R.W., Pitas R.E. Differential effects of apolipoproteins E3 and E4 on neuronal growth in vitro. Science (New York, N. Y.) 1994, 264:850-852.
86. Nicoll J.A., Burnett C., Love S., Graham D.I., Dewar D., Ironside J.W., Stewart J., Vinters H.V. High frequency of apolipoprotein E epsilon 2 allele in hemorrhage due to cerebral amyloid angiopathy. Annals of Neurology 1997, 41:716-721.
87. Ohm T.G., Scharnagl H., Marz W., Bohl J. Apolipoprotein E isoforms and the development of low and high Braak stages of Alzheimer's disease-related lesions. Acta Neuropathologica 1999, 98:273-280.
88. Oyama F., Shimada H., Oyama R., Ihara Y. Apolipoprotein E genotype, Alzheimer's pathologies and related gene expression in the aged population. Brain Research. Molecular Brain Research 1995, 29:92-98.
89. Pennanen C., Kivipelto M., Tuomainen S., Hartikainen P., Hanninen T., Laakso M.P., Hallikainen M., Vanhanen M., Nissinen A., Helkala E.L., Vainio P., Vanninen R., Partanen K., Soininen H. Hippocampus and entorhinal cortex in mild cognitive impairment and early AD. Neurobiology of Aging 2004, 25:303-310.
90. Permanne B., Perez C., Soto C., Frangione B., Wisniewski T. Detection of apolipoprotein E/dimeric soluble amyloid beta complexes in Alzheimer's disease brain supernatants. Biochemical and Biophysical Research Communications 1997, 240:715-720.
91. Pham T., Kodvawala A., Hui D.Y. The receptor binding domain of apolipoprotein E is responsible for its antioxidant activity. Biochemistry 2005, 44:7577-7582.
92. Polvikoski T., Sulkava R., Haltia M., Kainulainen K., Vuorio A., Verkkoniemi A., Niinisto L., Halonen P., Kontula K. Apolipoprotein E, dementia, and cortical deposition of beta-amyloid protein. The New England Journal of Medicine 1995, 333:1242-1247.
93. Puttonen S., Elovainio M., Kivimaki M., Lehtimaki T., Keltikangas-Jarvinen L. The combined effects of apolipoprotein E polymorphism and low-density lipoprotein cholesterol on cognitive performance in young adults. Neuropsychobiology 2003, 48:35-40.
94. Rea I.M., Mc Dowell I., McMaster D., Smye M., Stout R., Evans A. Apolipoprotein E alleles in nonagenarian subjects in the Belfast Elderly Longitudinal Free-living Ageing Study (BELFAST). Mechanisms of Ageing and Development 2001, 122:1367-1372.
95. Reinvang I., Espeseth T., Westlye L.T. APOE-related biomarker profiles in non-pathological aging and early phases of Alzheimer's disease. Neuroscience and Biobehavioral Reviews 2013, 37:1322-1335.
96. Rusted J.M., Evans S.L., King S.L., Dowell N., Tabet N., Tofts P.S. APOE e4 polymorphism in young adults is associated with improved attention and indexed by distinct neural signatures. NeuroImage 2013, 65:364-373.
97. Schachter F., Faure-Delanef L., Guenot F., Rouger H., Froguel P., Lesueur-Ginot L., Cohen D. Genetic associations with human longevity at the APOE and ACE loci. Nature Genetics 1994, 6:29-32.
98. Selkoe D.J. Clearing the brain's amyloid cobwebs. Neuron 2001, 32:177-180.
99. Serra-Grabulosa J.M., Salgado-Pineda P., Junque C., Sole-Padulles C., Moral P., Lopez-Alomar A., Lopez T., Lopez-Guillen A., Bargallo N., Mercader J.M., Clemente I.C., Bartres-Faz D. Apolipoproteins E and C1 and brain morphology in memory impaired elders. Neurogenetics 2003, 4:141-146.
100. Sharman M.J., Morici M., Hone E., Berger T., Taddei K., Martins I.J., Lim W.L., Singh S., Wenk M.R., Ghiso J., Buxbaum J.D., Gandy S., Martins R.N. APOE genotype results in differential effects on the peripheral clearance of amyloid-beta42 in APOE knock-in and knock-out mice. Journal of Alzheimer's Disease: JAD 2010, 21:403-409.
101. Shaw P., Lerch J.P., Pruessner J.C., Taylor K.N., Rose A.B., Greenstein D., Clasen L., Evans A., Rapoport J.L., Giedd J.N. Cortical morphology in children and adolescents with different apolipoprotein E gene polymorphisms: an observational study. Lancet Neurology 2007, 6:494-500.
102. Small G.W. Use of neuroimaging to detect early brain changes in people at genetic risk for Alzheimer's disease. Advanced Drug Delivery Reviews 2002, 54:1561-1566.
103. Staehelin H.B., Perrig-Chiello P., Mitrache C., Miserez A.R., Perrig W.J. Apolipoprotein E genotypes and cognitive functions in healthy elderly persons. Acta Neurologica Scandinavica 1999, 100:53-60.
104. Stebbins G.T., Murphy C.M. Diffusion tensor imaging in Alzheimer's disease and mild cognitive impairment. Behavioural Neurology 2009, 21:39-49.
105. Stoub T.R., Rogalski E.J., Leurgans S., Bennett D.A., deToledo-Morrell L. Rate of entorhinal and hippocampal atrophy in incipient and mild AD: relation to memory function. Neurobiology of Aging 2010, 31:1089-1098.
106. Strittmatter W.J., Saunders A.M., Goedert M., Weisgraber K.H., Dong L.M., Jakes R., Huang D.Y., Pericak-Vance M., Schmechel D., Roses A.D. Isoform-specific interactions of apolipoprotein E with microtubule-associated protein tau: implications for Alzheimer disease. Proceedings of the National Academy of Sciences of the United States of America 1994, 91:11183-11186.
107. Teter B., Xu P.T., Gilbert J.R., Roses A.D., Galasko D., Cole G.M. Human apolipoprotein E isoform-specific differences in neuronal sprouting in organotypic hippocampal culture. Journal of Neurochemistry 1999, 73:2613-2616.
108. Tiraboschi P., Hansen L.A., Masliah E., Alford M., Thal L.J., Corey-Bloom J. Impact of APOE genotype on neuropathologic and neurochemical markers of Alzheimer disease. Neurology 2004, 62:1977-1983.
109. Trachtenberg A.J., Filippini N., Cheeseman J., Duff E.P., Neville M.J., Ebmeier K.P., Karpe F., Mackay C.E. The effects of APOE on brain activity do not simply reflect the risk of Alzheimer's disease. Neurobiology of Aging 2012, 33. 618.e611-618.e613.
110. Trachtenberg A.J., Filippini N., Ebmeier K.P., Smith S.M., Karpe F., Mackay C.E. The effects of APOE on the functional architecture of the resting brain. NeuroImage 2012, 59:565-572.
111. Trachtenberg A.J., Filippini N., Mackay C.E. The effects of APOE-epsilon4 on the BOLD response. Neurobiology of Aging 2012, 33:323-334.
112. Trommer B.L., Shah C., Yun S.H., Gamkrelidze G., Pasternak E.S., Ye G.L., Sotak M., Sullivan P.M., Pasternak J.F., LaDu M.J. ApoE isoform affects LTP in human targeted replacement mice. Neuroreport 2004, 15:2655-2658.
113. Tuminello E.R., Han S.D. The apolipoprotein e antagonistic pleiotropy hypothesis: review and recommendations. International Journal of Alzheimer's Disease 2011, 2011:726197.
114. Verpillat P., Camuzat A., Hannequin D., Thomas-Anterion C., Puel M., Belliard S., Dubois B., Didic M., Lacomblez L., Moreaud O., Golfier V., Campion D., Brice A., Clerget-Darpoux F. Apolipoprotein E gene in frontotemporal dementia: an association study and meta-analysis. European Journal of Human Genetics: EJHG 2002, 10:399-405.
115. Weisgraber K.H., Rall S.C., Mahley R.W. Human E apoprotein heterogeneity. Cysteine-arginine interchanges in the amino acid sequence of the apo-E isoforms. The Journal of Biological Chemistry 1981, 256:9077-9083.
116. Westlye L.T., Reinvang I., Rootwelt H., Espeseth T. Effects of APOE on brain white matter microstructure in healthy adults. Neurology 2012, 79:1961-1969.
117. Wilson R.S., Bienias J.L., Berry-Kravis E., Evans D.A., Bennett D.A. The apolipoprotein E epsilon 2 allele and decline in episodic memory. Journal of Neurology, Neurosurgery, and Psychiatry 2002, 73:672-677.
118. Wisniewski T., Frangione B. Apolipoprotein E: a pathological chaperone protein in patients with cerebral and systemic amyloid. Neuroscience Letters 1992, 135:235-238.
119. Xu Q., Brecht W.J., Weisgraber K.H., Mahley R.W., Huang Y. Apolipoprotein E4 domain interaction occurs in living neuronal cells as determined by fluorescence resonance energy transfer. The Journal of Biological Chemistry 2004, 279:25511-25516.
120. Yang D.S., Smith J.D., Zhou Z., Gandy S.E., Martins R.N. Characterization of the binding of amyloid-beta peptide to cell culture-derived native apolipoprotein E2, E3, and E4 isoforms and to isoforms from human plasma. Journal of Neurochemistry 1997, 68:721-725.
121. Yu Y.W., Lin C.H., Chen S.P., Hong C.J., Tsai S.J. Intelligence and event-related potentials for young female human volunteer apolipoprotein E epsilon4 and non-epsilon4 carriers. Neuroscience Letters 2000, 294:179-181.
122. Zannis V.I., Just P.W., Breslow J.L. Human apolipoprotein E isoprotein subclasses are genetically determined. American Journal of Human Genetics 1981, 33:11-24.
123. Zhong N., Weisgraber K.H. Understanding the association of apolipoprotein E4 with Alzheimer disease: clues from its structure. The Journal of Biological Chemistry 2009, 284:6027-6031.
124. Zhu Y., Nwabuisi-Heath E., Dumanis S.B., Tai L.M., Yu C., Rebeck G.W., LaDu M.J. APOE genotype alters glial activation and loss of synaptic markers in mice. Glia 2012, 60:559-569.