title: Dietary omega 3 polyunsaturated fatty acids and Alzheimer's disease: interaction with apolipoprotein E genotype.
abstract: Epidemiological studies suggest a protective role of omega-3 poly-unsaturated fatty acids (n-3 PUFA) against Alzheimer's disease (AD). However, most intervention studies of supplementation with n-3 PUFA have yielded disappointing results. One reason for such discordant results may result from inadequate targeting of individuals who might benefit from the supplementation, in particular because of their genetic susceptibility to AD. The ε4 allele of the apolipoprotein E gene (ApoE) is a genetic risk factor for late-onset AD. ApoE plays a key role in the transport of cholesterol and other lipids involved in brain composition and functioning. The action of n-3 PUFA on the aging brain might therefore differ according to ApoE polymorphism. The aim of this review is to examine the interaction between dietary fatty acids and ApoE genotype on the risk for AD. Carriers of the ε4 allele tend to be the most responsive to changes in dietary fat and cholesterol. Conversely, several epidemiological studies suggest a protective effect of long-chain n-3 PUFA on cognitive decline only in those who do not carry ε4 but with inconsistent results. An intervention study showed that only non-carriers had increased concentrations of long-chain n-3 PUFA in response to supplementation. The mechanisms underlying this gene-by-diet interaction on AD risk may involve impaired fatty acids and cholesterol transport, altered metabolism of n-3 PUFA, glucose or ketones, or modification of other risk factors of AD in ε4 carriers. Further research is needed to explain the differential effect of n-3 PUFA on AD according to ApoE genotype.
authors: Inserm, U897, Bordeaux, F-33076 France. Pascale.Barberger-Gateau@isped.u-bordeaux2.fr
authors: P
authors: P
authors: Barberger-Gateau
authors: C
authors: C
authors: Samieri
authors: C
authors: C
authors: Féart
authors: M
authors: M
authors: Plourde
references: Brain Res. 2002 Jan 4;924(1):90-7
references: 11743999
references: J Am Geriatr Soc. 2008 Jan;56(1):111-6
references: 18028342
references: J Mol Neurosci. 2007 Sep;33(1):12-7
references: 17901540
references: Arch Neurol. 2007 Jan;64(1):103-7
references: 17210816
references: Neuron. 2009 Aug 13;63(3):287-303
references: 19679070
references: Prog Lipid Res. 2008 Mar;47(2):127-46
references: 18177744
references: Prostaglandins Leukot Essent Fatty Acids. 2007 Nov-Dec;77(5-6):301-8
references: 18036804
references: Am J Epidemiol. 2008 Nov 15;168(10):1179-89
references: 18835864
references: Clin Chem. 1999 Aug;45(8 Pt 1):1214-23
references: 10430787
references: Ann Neurol. 2009 Jun;65(6):650-7
references: 19557866
references: J Neural Transm (Vienna). 2009 Nov;116(11):1427-34
references: 19370389
references: J Nutr. 2008 Dec;138(12):2515-20
references: 19022981
references: Dement Geriatr Cogn Disord. 2009;28(1):75-80
references: 19648749
references: J Clin Invest. 1967 Oct;46(10):1589-95
references: 6061736
references: Br J Nutr. 2009 Oct;102(8):1121-4
references: 19828088
references: Prog Lipid Res. 2009 Sep;48(5):239-56
references: 19362576
references: Am J Clin Nutr. 2008 Feb;87(2):449-54
references: 18258638
references: Endocrinology. 2008 May;149(5):2628-36
references: 18276751
references: J Affect Disord. 2009 Jun;115(3):471-7
references: 18990452
references: JAMA. 1997 Oct 22-29;278(16):1349-56
references: 9343467
references: Proc Nutr Soc. 2007 Feb;66(1):60-8
references: 17343773
references: Neurobiol Aging. 2007 Dec;28(12):1810-20
references: 17011077
references: BMJ. 2002 Oct 26;325(7370):932-3
references: 12399342
references: Am J Clin Nutr. 2009 Jul;90(1):170-6
references: 19474131
references: FEBS J. 2009 Oct;276(20):5720-8
references: 19754875
references: Neurosci Lett. 2009 May 15;455(2):116-9
references: 19368858
references: Am J Clin Nutr. 2008 May;87(5):1156-62
references: 18469234
references: Arch Neurol. 2005 Oct;62(10):1556-60
references: 16216938
references: Neurology. 2007 Mar 6;68(10):751-6
references: 17339582
references: Nutr Metab (Lond). 2009 Aug 10;6:31
references: 19664276
references: Am J Clin Nutr. 2007 Nov;86(5):1384-91
references: 17991650
references: J Neurosci. 2009 Oct 14;29(41):12795-801
references: 19828791
references: J Nutr Health Aging. 2005;9(1):31-8
references: 15750663
references: Annu Rev Genomics Hum Genet. 2000;1:507-37
references: 11701639
references: Neurology. 2002 Dec 24;59(12):1915-21
references: 12499483
references: Obes Rev. 2008 May;9(3):204-18
references: 18331422
references: Neurosci Lett. 1999 Dec 17;277(1):53-6
references: 10643896
references: J Lipid Res. 2003 Nov;44(11):2065-72
references: 12923230
references: Am J Clin Nutr. 2009 Feb;89(2):641-51
references: 19116322
references: Neurobiol Aging. 2009 Apr;30(4):534-45
references: 17888546
references: Neurology. 2009 Dec 15;73(24):2054-5
references: 20007523
references: Alzheimers Dement. 2010 Nov;6(6):456-64
references: 20434961
references: J Cell Mol Med. 2007 Nov-Dec;11(6):1227-38
references: 18205697
references: Lancet Neurol. 2005 Dec;4(12):841-52
references: 16297842
references: J Mol Neurosci. 2007 Sep;33(1):2-11
references: 17901539
references: Am J Clin Nutr. 2010 Jun;91(6):1725-32
references: 20410089
references: Diabetes Care. 2009 Jan;32(1):169-74
references: 18945929
references: Neurology. 2008 Jan 1;70(1):17-24
references: 18003940
references: Lancet. 1998 Apr 18;351(9110):1213
references: 9643729
references: J Mol Neurosci. 2001 Apr-Jun;16(2-3):159-65; discussion 215-21
references: 11478370
references: Am J Clin Nutr. 1995 Dec;62(6):1193-200
references: 7491879
references: Br J Nutr. 2009 Nov;102(9):1370-4
references: 19454127
references: Alzheimer Dis Assoc Disord. 2006 Apr-Jun;20(2):112-7
references: 16772747
references: Am J Clin Nutr. 2008 Sep;88(3):618-29
references: 18779276
references: Am J Clin Nutr. 2003 Jul;78(1):40-6
references: 12816769
references: Gerontology. 2000 Jul-Aug;46(4):219-27
references: 10859462
references: J Mol Neurosci. 2001 Apr-Jun;16(2-3):181-93; discussion 215-21
references: 11478373
references: Int J Geriatr Psychiatry. 2008 Feb;23(2):161-9
references: 17582225
references: Eur J Clin Nutr. 1994 Dec;48(12):866-72
references: 7889895
references: Prostaglandins Leukot Essent Fatty Acids. 2008 Mar;78(3):171-82
references: 18329261
references: Neurobiol Aging. 2007 Dec;28(12):1834-9
references: 16996649
references: Am J Clin Nutr. 2009 Feb;89(2):601-7
references: 19073790
references: Neurology. 2005 Nov 8;65(9):1409-14
references: 16275829
references: Coron Artery Dis. 1993 Jan;4(1):53-60
references: 8269183
references: Clin Endocrinol (Oxf). 2006 Mar;64(3):265-70
references: 16487435
references: Acta Neurol Scand. 1999 Jul;100(1):53-60
references: 10416512
references: Neurology. 2007 Nov 13;69(20):1921-30
references: 17998483
references: JAMA. 2002 Jun 26;287(24):3230-7
references: 12076219
references: N Engl J Med. 2010 Jan 28;362(4):329-44
references: 20107219
references: Drugs Aging. 2003;20(6):399-418
references: 12710861
references: Biochem Biophys Res Commun. 1998 Nov 27;252(3):711-5
references: 9837771
references: Appl Physiol Nutr Metab. 2007 Aug;32(4):619-34
references: 17622276
references: J Nutr Health Aging. 2009 Apr;13(4):293-8
references: 19300863
references: Ann Neurol. 2005 Nov;58(5):730-5
references: 16240347
references: Nutrition. 2010 Jan;26(1):112-9
references: 19815389
references: Dement Geriatr Cogn Disord. 2006;22(1):99-107
references: 16710090
references: N Engl J Med. 2002 Feb 14;346(7):476-83
references: 11844848
references: Am J Clin Nutr. 2007 Apr;85(4):1103-11
references: 17413112
references: Dement Geriatr Cogn Disord. 2009;27(5):481-90
references: 19439966
references: Atherosclerosis. 2010 Mar;209(1):104-10
references: 19748619
references: Am J Clin Nutr. 2007 Feb;85(2):511-7
references: 17284751
references: Neurology. 2005 May 10;64(9):1531-8
references: 15883313
references: Am J Clin Nutr. 2005 Mar;81(3):624-32
references: 15755832
references: Arch Neurol. 2002 Aug;59(8):1258-63
references: 12164721
references: Arch Neurol. 2010 Jan;67(1):87-92
references: 20065134
references: J Clin Psychiatry. 2007 Jul;68(7):1056-61
references: 17685742
references: Proc Nutr Soc. 2007 May;66(2):183-97
references: 17466101
references: Neurobiol Aging. 2011 Dec;32(12):2317.e13-22
references: 20570406
references: Arch Neurol. 2004 Aug;61(8):1290-3
references: 15313849
references: Arch Neurol. 2003 Jul;60(7):940-6
references: 12873849
references: Dement Geriatr Cogn Disord. 2006;21(3):198-204
references: 16407653
references: Clin Chim Acta. 2006 Feb;364(1-2):91-112
references: 16139826
references: Am J Clin Nutr. 2006 Dec;84(6):1473-80
references: 17158432
references: Am J Clin Nutr. 2003 May;77(5):1098-111
references: 12716659
references: J Nutr. 2009 Oct;139(10):1944-9
references: 19675102
references: Br J Nutr. 2008 Feb;99(2):421-31
references: 17956647
references: J Nutr. 2006 Dec;136(12):2965-9
references: 17116704
references: Neurosci Res. 2006 Oct;56(2):159-64
references: 16905216
references: Mol Nutr Food Res. 2008 Jan;52(1):131-45
references: 18203129
references: Neurobiol Aging. 2004 Mar;25(3):311-4
references: 15123336
references: Ann Neurol. 1997 Nov;42(5):776-82
references: 9392577
references: Arch Neurol. 2006 Oct;63(10):1402-8
references: 17030655
references: Am J Geriatr Psychiatry. 2008 Sep;16(9):781-5
references: 18757771
references: Clin Biochem. 2008 Aug;41(12):932-6
references: 18505684
references: Genes Immun. 2006 Apr;7(3):211-9
references: 16511556
references: Curr Alzheimer Res. 2007 Apr;4(2):185-9
references: 17430245
references: Neurobiol Aging. 2009 Jan;30(1):112-24
references: 17630048
references: JAMA. 2010 Nov 3;304(17):1903-11
references: 21045096
references: Lancet. 2006 Jul 29;368(9533):387-403
references: 16876668
references: J Lipid Res. 2005 May;46(5):949-68
references: 15716586
references: Am J Clin Nutr. 2009 Jul;90(1):184-92
references: 19474137
references: Psychiatr Serv. 2001 Apr;52(4):529-31
references: 11274502
references: Prog Neuropsychopharmacol Biol Psychiatry. 2008 Aug 1;32(6):1538-44
references: 18573585
references: J Nutr. 2009 Dec;139(12):2329-36
references: 19828689
references: Neurology. 2006 Jan 24;66(2):223-7
references: 16434658
references: J Gerontol A Biol Sci Med Sci. 2006 Jun;61(6):616-20
references: 16799145
references: Ann Intern Med. 2002 Aug 6;137(3):149-55
references: 12160362
references: J Am Geriatr Soc. 2009 Jan;57(1):11-7
references: 19054188
references: Prog Lipid Res. 2008 Mar;47(2):147-55
references: 18198131
references: Nat Genet. 1996 Sep;14(1):55-61
references: 8782820
references: Neurology. 2009 Sep 8;73(10):768-74
references: 19738171
references: J Nutr. 2008 Dec;138(12):2510-4
references: 19022980
references: J Neurosci Res. 2003 Mar 15;71(6):863-70
references: 12605413
references: J Mol Neurosci. 2007 Sep;33(1):56-66
references: 17901547
references: Am J Clin Nutr. 2008 Sep;88(3):714-21
references: 18779288
references: Prostaglandins Leukot Essent Fatty Acids. 2007 May;76(5):293-7
references: 17466498
references: Public Health Nutr. 2009 Dec;12(12):2371-6
references: 19278567
references: Neurosci Lett. 2008 Jan 3;430(1):64-9
references: 18023533
references: Prog Lipid Res. 2004 Mar;43(2):105-33
references: 14654090
references: Eur J Pharmacol. 2008 May 6;585(1):176-96
references: 18378224
references: J Cell Mol Med. 2008 Dec;12(6B):2762-71
references: 18318693
references: Am J Clin Nutr. 2005 Sep;82(3):636-43
references: 16155278
references: Int J Food Sci Nutr. 2008 Sep;59(6):491-501
references: 18686110
references: Am J Clin Nutr. 2009 Jul;90(1):49-55
references: 19474136
references: Free Radic Biol Med. 2002 Sep 1;33(5):620-6
references: 12208348
references: J Neurol. 2005 May;252(5):548-58
references: 15726251
references: Am J Clin Nutr. 2008 Sep;88(3):706-13
references: 18779287
references: Mol Cell Biochem. 2010 Apr;337(1-2):307-15
references: 19915960
references: Dement Geriatr Cogn Disord. 2000 Mar-Apr;11(2):70-3
references: 10705163
references: Nat Rev Neurol. 2009 Dec;5(12):649-58
references: 19918254
references: Neurology. 2001 Mar 13;56(5):655-9
references: 11245719
references: Proc Natl Acad Sci U S A. 2006 Apr 11;103(15):5644-51
references: 16567625
references: Arch Neurol. 2009 Mar;66(3):336-42
references: 19273752
references: Neurology. 2003 Jan 14;60(1):117-9
references: 12525731
references: Nat Genet. 2009 Oct;41(10):1094-9
references: 19734903
references: Arch Neurol. 2009 Mar;66(3):329-35
references: 19273751
references: Proc Natl Acad Sci U S A. 2004 Jan 6;101(1):284-9
references: 14688411
references: Am J Clin Nutr. 2009 Aug;90(2):392-400
references: 19553298
references: Am J Clin Nutr. 2005 Sep;82(3):627-35
references: 16155277
references: Neurology. 2009 Apr 28;72(17):1487-94
references: 19339712
references: Int J Geriatr Psychiatry. 2008 Sep;23(9):922-8
references: 18327871
references: Neurology. 2008 Aug 5;71(6):430-8
references: 18678826
references: Neurology. 2000 Jan 11;54(1):240-2
references: 10636159
references: Neurochem Res. 2010 Mar;35(3):503-13
references: 19904605
references: J Nutr. 2010 Apr;140(4):869-74
references: 20181786
references: Neurology. 2008 Sep 30;71(14):1057-64
references: 18367704