Association of Docosahexaenoic Acid Supplementation With Alzheimer Disease Stage in Apolipoprotein E ε4 Carriers: A Review.
Authors:
Journal: JAMA neurology
Publication Type: Journal Article
Date: 2017
DOI: NIHMS939985
ID: 28114437
Abstract
The apolipoprotein E ε4 (APOE4) allele identifies a unique population that is at significant risk for developing Alzheimer disease (AD). Docosahexaenoic acid (DHA) is an essential ω-3 fatty acid that is critical to the formation of neuronal synapses and membrane fluidity. Observational studies have associated ω-3 intake, including DHA, with a reduced risk for incident AD. In contrast, randomized clinical trials of ω-3 fatty acids have yielded mixed and inconsistent results. Interactions among DHA, APOE genotype, and stage of AD pathologic changes may explain the mixed results of DHA supplementation reported in the literature.
Chemical List
- Apolipoprotein E4|||Docosahexaenoic Acids
Reference List
- Lambert J-C, Ibrahim-Verbaas CA, Harold D, et al. European Alzheimer’s Disease Initiative (EADI); Genetic and Environmental Risk in Alzheimer’s Disease; Alzheimer’s Disease Genetic Consortium; Cohorts for Heart and Aging Research in Genomic Epidemiology Meta-analysis of 74,046 individuals identifies 11 new susceptibility loci for Alzheimer’s disease. Nat Genet. 2013;45(12):1452–1458.|||Corder EH, Saunders AM, Strittmatter WJ, et al. Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer’s disease in late onset families. Science. 1993;261(5123):921–923.|||Castellano JM, Kim J, Stewart FR, et al. Human apoE isoforms differentially regulate brain amyloid-β peptide clearance. Sci Transl Med. 2011;3(89):89ra57.|||Friedman G, Froom P, Sazbon L, et al. Apolipoprotein E-ε4 genotype predicts a poor outcome in survivors of traumatic brain injury. Neurology. 1999;52(2):244–248.|||Egensperger R, Kösel S, von Eitzen U, Graeber MB. Microglial activation in Alzheimer disease: association with APOE genotype. Brain Pathol. 1998;8(3):439–447.|||Zlokovic BV. Cerebrovascular effects of apolipoprotein E: implications for Alzheimer disease. JAMA Neurol. 2013;70(4):440–444.|||Rapoport SI, Igarashi M. Can the rat liver maintain normal brain DHA metabolism in the absence of dietary DHA? Prostaglandins Leukot Essent Fatty Acids. 2009;81(2–3):119–123.|||Grimm MO, Kuchenbecker J, Grösgen S, et al. Docosahexaenoic acid reduces amyloid β production via multiple pleiotropic mechanisms. J Biol Chem. 2011;286(16):14028–14039.|||Hooijmans CR, Rutters F, Dederen PJ, et al. Changes in cerebral blood volume and amyloid pathology in aged Alzheimer APP/PS1 mice on a docosahexaenoic acid (DHA) diet or cholesterol enriched typical western diet (TWD) Neurobiol Dis. 2007;28(1):16–29.|||Söderberg M, Edlund C, Kristensson K, Dallner G. Fatty acid composition of brain phospholipids in aging and in Alzheimer’s disease. Lipids. 1991;26(6):421–425.|||Hooijmans CR, Pasker-de Jong PC, de Vries RB, Ritskes-Hoitinga M. The effects of long-term omega-3 fatty acid supplementation on cognition and Alzheimer’s pathology in animal models of Alzheimer’s disease: a systematic review and meta-analysis. J Alzheimers Dis. 2012;28(1):191–209.|||Zhang Y, Chen J, Qiu J, Li Y, Wang J, Jiao J. Intakes of fish and polyunsaturated fatty acids and mild-to-severe cognitive impairment risks: a dose-response meta-analysis of 21 cohort studies. Am J Clin Nutr. 2016;103(2):330–340.|||Quinn JF, Raman R, Thomas RG, et al. Docosahexaenoic acid supplementation and cognitive decline in Alzheimer disease: a randomized trial. JAMA. 2010;304(17):1903–1911.|||Freund-Levi Y, Eriksdotter-Jönhagen M, Cederholm T, et al. Omega-3 fatty acid treatment in 174 patients with mild to moderate Alzheimer disease: OmegAD study: a randomized double-blind trial. Arch Neurol. 2006;63(10):1402–1408.|||van de Rest O, Geleijnse JM, Kok FJ, et al. Effect of fish oil on cognitive performance in older subjects: a randomized, controlled trial. Neurology. 2008;71(6):430–438.|||Chiu C-C, Su K-P, Cheng T-C, et al. The effects of omega-3 fatty acids monotherapy in Alzheimer’s disease and mild cognitive impairment: a preliminary randomized double-blind placebo-controlled study. Prog Neuropsychopharmacol Biol Psychiatry. 2008;32(6):1538–1544.|||Lee LK, Shahar S, Chin A-V, Yusoff NAM. Docosahexaenoic acid–concentrated fish oil supplementation in subjects with mild cognitive impairment (MCI): a 12-month randomised, double-blind, placebo-controlled trial. Psychopharmacology (Berl) 2013;225(3):605–612.|||Sinn N, Milte CM, Street SJ, et al. Effects of n-3 fatty acids, EPA v DHA, on depressive symptoms, quality of life, memory and executive function in older adults with mild cognitive impairment: a 6-month randomised controlled trial. Br J Nutr. 2012;107(11):1682–1693.|||Stonehouse W, Conlon CA, Podd J, et al. DHA supplementation improved both memory and reaction time in healthy young adults: a randomized controlled trial. Am J Clin Nutr. 2013;97(5):1134–1143.|||Külzow N, Witte AV, Kerti L, et al. Impact of omega-3 fatty acid supplementation on memory functions in healthy older adults. J Alzheimers Dis. 2016;51(3):713–725.|||Benton D, Donohoe RT, Clayton DE, Long SJ. Supplementation with DHA and the psychological functioning of young adults. Br J Nutr. 2013;109(1):155–161.|||Jackson PA, Deary ME, Reay JL, Scholey AB, Kennedy DO. No effect of 12 weeks’ supplementation with 1 g DHA-rich or EPA-rich fish oil on cognitive function or mood in healthy young adults aged 18–35 years. Br J Nutr. 2012;107(8):1232–1243.|||Yurko-Mauro K, McCarthy D, Rom D, et al. MIDAS Investigators Beneficial effects of docosahexaenoic acid on cognition in age-related cognitive decline. Alzheimers Dement. 2010;6(6):456–464.|||Johnson EJ, McDonald K, Caldarella SM, Chung HY, Troen AM, Snodderly DM. Cognitive findings of an exploratory trial of docosahexaenoic acid and lutein supplementation in older women. Nutr Neurosci. 2008;11(2):75–83.|||Dangour AD, Allen E, Elbourne D, et al. Effect of 2-y ω-3 long-chain polyunsaturated fatty acid supplementation on cognitive function in older people: a randomized, double-blind, controlled trial. Am J Clin Nutr. 2010;91(6):1725–1732.|||Geleijnse JM, Giltay EJ, Kromhout D. Effects of ω-3 fatty acids on cognitive decline: a randomized, double-blind, placebo-controlled trial in stable myocardial infarction patients. Alzheimers Dement. 2012;8(4):278–287.|||Sydenham E, Dangour AD, Lim WS. Omega 3 fatty acid for the prevention of cognitive decline and dementia. Cochrane Database Syst Rev. 2012;(6):CD005379.|||Yurko-Mauro K, Alexander DD, Van Elswyk ME. Docosahexaenoic acid and adult memory: a systematic review and meta-analysis. PLoS One. 2015;10(3):e0120391.|||Cao D, Kevala K, Kim J, et al. Docosahexaenoic acid promotes hippocampal neuronal development and synaptic function. J Neurochem. 2009;111(2):510–521.|||Salem N, Jr, Moriguchi T, Greiner RS, et al. Alterations in brain function after loss of docosahexaenoate due to dietary restriction of n-3 fatty acids. J Mol Neurosci. 2001;16(2–3):299–307.|||Kariv-Inbal Z, Yacobson S, Berkecz R, et al. The isoform-specific pathological effects of APOE4 in vivo are prevented by a fish oil (DHA) diet and are modified by cholesterol. J Alzheimers Dis. 2012;28(3):667–683.|||Huang TL, Zandi PP, Tucker KL, et al. Benefits of fatty fish on dementia risk are stronger for those without APOE ε4. Neurology. 2005;65(9):1409–1414.|||Barberger-Gateau P, Raffaitin C, Letenneur L, et al. Dietary patterns and risk of dementia: the Three-City cohort study. Neurology. 2007;69(20):1921–1930.|||Whalley LJ, Deary IJ, Starr JM, et al. ω-3 Fatty acid erythrocyte membrane content, APOE varepsilon4, and cognitive variation: an observational follow-up study in late adulthood. Am J Clin Nutr. 2008;87(2):449–454.|||Daiello LA, Gongvatana A, Dunsiger S, Cohen RA, Ott BR, Alzheimer’s Disease Neuroimaging Initiative Association of fish oil supplement use with preservation of brain volume and cognitive function. Alzheimers Dement. 2015;11(2):226–235.|||Laitinen MH, Ngandu T, Rovio S, et al. Fat intake at midlife and risk of dementia and Alzheimer’s disease: a population-based study. Dement Geriatr Cogn Disord. 2006;22(1):99–107.|||Morris MC, Brockman J, Schneider JA, et al. Association of seafood consumption, brain mercury level, and APOE ε4 status with brain neuropathology in older adults. JAMA. 2016;315(5):489–497.|||Samieri C, Féart C, Proust-Lima C, et al. ω-3 Fatty acids and cognitive decline: modulation by APOEε4 allele and depression. Neurobiol Aging. 2011;32(12):2317.e13–2317.e22.|||Vellas B, Voisin T, Dufouil C, et al. MAPT (Multi-Domain Alzheimer’s Prevention Trial): clinical biomarkers, results and lessons for the future [abstract OC33] J Prev Alzheimers Dis. 2015;2(4):292.|||Beydoun MA, Kaufman JS, Satia JA, Rosamond W, Folsom AR. Plasma ω-3 fatty acids and the risk of cognitive decline in older adults: the Atherosclerosis Risk in Communities Study. Am J Clin Nutr. 2007;85(4):1103–1111.|||Kröger E, Verreault R, Carmichael PH, et al. Omega-3 fatty acids and risk of dementia: the Canadian Study of Health and Aging. Am J Clin Nutr. 2009;90(1):184–192.|||Rönnemaa E, Zethelius B, Vessby B, Lannfelt L, Byberg L, Kilander L. Serum fatty-acid composition and the risk of Alzheimer’s disease: a longitudinal population-based study. Eur J Clin Nutr. 2012;66(8):885–890.|||Yassine HN, Feng Q, Azizkhanian I, et al. Association of serum docosahexaenoic acid with cerebral amyloidosis. JAMA Neurol. 2016;73(10):1208–1216.|||Yassine HN, Rawat V, Mack WJ, et al. The effect of APOE genotype on the delivery of DHA to cerebrospinal fluid in Alzheimer’s disease. Alzheimers Res Ther. 2016;8:25.|||Vandal M, Alata W, Tremblay C, et al. Reduction in DHA transport to the brain of mice expressing human APOE4 compared to APOE2. J Neurochem. 2014;129(3):516–526.|||Mahley RW, Weisgraber KH, Huang Y. Apolipoprotein E: structure determines function, from atherosclerosis to Alzheimer’s disease to AIDS. J Lipid Res. 2009;50(suppl):S183–S188.|||Polozova A, Salem N., Jr Role of liver and plasma lipoproteins in selective transport of ω-3 fatty acids to tissues: a comparative study of 14C-DHA and 3H-oleic acid tracers. J Mol Neurosci. 2007;33(1):56–66.|||Weisgraber KH. Apolipoprotein E distribution among human plasma lipoproteins: role of the cysteine-arginine interchange at residue 112. J Lipid Res. 1990;31(8):1503–1511.|||Chouinard-Watkins R, Rioux-Perreault C, Fortier M, et al. Disturbance in uniformly 13C-labelled DHA metabolism in elderly human subjects carrying the APOE ε4 allele. Br J Nutr. 2013;110(10):1751–1759.|||Calon F. Omega-3 polyunsaturated fatty acids in Alzheimer’s disease: key questions and partial answers. Curr Alzheimer Res. 2011;8(5):470–478.|||Halliday MR, Pomara N, Sagare AP, Mack WJ, Frangione B, Zlokovic BV. Relationship between cyclophilin A levels and matrix metalloproteinase 9 activity in cerebrospinal fluid of cognitively normal apolipoprotein e4 carriers and blood-brain barrier breakdown. JAMA Neurol. 2013;70(9):1198–1200.|||Nguyen LN, Ma D, Shui G, et al. Mfsd2a is a transporter for the essential omega-3 fatty acid docosahexaenoic acid. Nature. 2014;509(7501):503–506.|||Fu Y, Zhao J, Atagi Y, et al. Apolipoprotein E lipoprotein particles inhibit amyloid-β uptake through cell surface heparan sulphate proteoglycan. Mol Neurodegener. 2016;11(1):37.|||Boehm-Cagan A, Michaelson DM. Reversal of APOE4-driven brain pathology and behavioral deficits by bexarotene. J Neurosci. 2014;34(21):7293–7301.|||Yassine HN, Feng Q, Chiang J, et al. ABCA1-mediated cholesterol efflux capacity to cerebrospinal fluid is reduced in patients with mild cognitive impairment and Alzheimer’s disease. J Am Heart Assoc. 2016;5(2):e002886.|||Klosinski LP, Yao J, Yin F, et al. White matter lipids as a ketogenic fuel supply in aging female brain: implications for Alzheimer’s disease. EBioMedicine. 2015;2(12):1888–1904.|||Reich EE, Markesbery WR, Roberts LJ, II, Swift LL, Morrow JD, Montine TJ. Brain regional quantification of F-ring and D-/E-ring isoprostanes and neuroprostanes in Alzheimer’s disease. Am J Pathol. 2001;158(1):293–297.|||Palop JJ, Chin J, Roberson ED, et al. Aberrant excitatory neuronal activity and compensatory remodeling of inhibitory hippocampal circuits in mouse models of Alzheimer’s disease. Neuron. 2007;55(5):697–711.|||Sanchez-Mejia RO, Newman JW, Toh S, et al. Phospholipase A2 reduction ameliorates cognitive deficits in a mouse model of Alzheimer’s disease. Nat Neurosci. 2008;11(11):1311–1318.|||Fonteh AN, Chiang J, Cipolla M, et al. Alterations in cerebrospinal fluid glycerophospholipids and phospholipase A2 activity in Alzheimer’s disease. J Lipid Res. 2013;54(10):2884–2897.|||Caselli RJ, Dueck AC, Osborne D, et al. Longitudinal modeling of age-related memory decline and the APOE ε4 effect. N Engl J Med. 2009;361(3):255–263.|||Vellas B, Voisin T, Dufouil CI, et al. MAPT study: a multidomain approach for preventing Alzheimer’s disease: design and baseline data. J Prev Alzheimers Dis. 2014;1(1):13–22.|||Umhau JC, Zhou W, Carson RE, et al. Imaging incorporation of circulating docosahexaenoic acid into the human brain using positron emission tomography. J Lipid Res. 2009;50(7):1259–1268.|||Umhau JC, Zhou W, Thada S, et al. Brain docosahexaenoic acid [DHA] incorporation and blood flow are increased in chronic alcoholics: a positron emission tomography study corrected for cerebral atrophy. PLoS One. 2013;8(10):e75333.|||Morris JC, Roe CM, Xiong C, et al. APOE predicts Aβ but not tau Alzheimer pathology in cognitively normal aging. Ann Neurol. 2010;67(1):122–131.|||Reiman EM, Chen K, Alexander GE, et al. Functional brain abnormalities in young adults at genetic risk for late-onset Alzheimer’s dementia. Proc Natl Acad Sci U S A. 2004;101(1):284–289.|||de Leon MJ, Convit A, Wolf OT, et al. Prediction of cognitive decline in normal elderly subjects with 2-[18F]fluoro-2-deoxy-D-glucose/positron-emission tomography (FDG/PET) Proc Natl Acad Sci U S A. 2001;98(19):10966–10971.|||Pifferi F, Dorieux O, Castellano CA, et al. Long-chain ω-3 PUFAs from fish oil enhance resting state brain glucose utilization and reduce anxiety in an adult nonhuman primate, the grey mouse lemur. J Lipid Res. 2015;56(8):1511–1518.|||Sheline YI, Morris JC, Snyder AZ, et al. APOE4 allele disrupts resting state fMRI connectivity in the absence of amyloid plaques or decreased CSF Aβ42. J Neurosci. 2010;30(50):17035–17040.|||Greicius MD, Srivastava G, Reiss AL, Menon V. Default-mode network activity distinguishes Alzheimer’s disease from healthy aging: evidence from functional MRI. Proc Natl Acad Sci U S A. 2004;101(13):4637–4642.|||Chang PK, Khatchadourian A, McKinney RA, Maysinger D. Docosahexaenoic acid (DHA): a modulator of microglia activity and dendritic spine morphology. J Neuroinflammation. 2015;12:34.|||Thomas J, Thomas CJ, Radcliffe J, Itsiopoulos C. Omega-3 fatty acids in early prevention of inflammatory neurodegenerative disease: a focus on Alzheimer’s disease. Biomed Res Int. 2015;2015:172801.|||Witte AV, Kerti L, Hermannstädter HM, et al. Long-chain omega-3 fatty acids improve brain function and structure in older adults. Cereb Cortex. 2014;24(11):3059–3068.|||Liu DS, Pan XD, Zhang J, et al. APOE4 enhances age-dependent decline in cognitive function by down-regulating an NMDA receptor pathway in EFAD-Tg mice. Mol Neurodegener. 2015;10:7.|||Burggren AC, Zeineh MM, Ekstrom AD, et al. Reduced cortical thickness in hippocampal subregions among cognitively normal apolipoprotein E e4 carriers. Neuroimage. 2008;41(4):1177–1183.