Carriers of an apolipoprotein E epsilon 4 allele are more vulnerable to a dietary deficiency in omega-3 fatty acids and cognitive decline

Tanya Gwendolyn Nock, Raphaël Chouinard-Watkins, Mélanie Plourde

Tài liệu tham khảo

Zlokovic, 2013, Cerebrovascular effects of apolipoprotein E: implications for Alzheimer disease, JAMA Neurol., 70, 440, 10.1001/jamaneurol.2013.2152 Kok, 2009, Apolipoprotein E-dependent accumulation of Alzheimer disease-related lesions begins in middle age, Ann. Neurol., 65, 650, 10.1002/ana.21696 Montagne, 2015, Blood-brain barrier breakdown in the aging human hippocampus, Neuron, 85, 296, 10.1016/j.neuron.2014.12.032 Ben-Zvi, 2014, Mfsd2a is critical for the formation and function of the blood-brain barrier, Nature, 509, 507, 10.1038/nature13324 Nguyen, 2014, Mfsd2a is a transporter for the essential omega-3 fatty acid docosahexaenoic acid, Nature, 509, 503, 10.1038/nature13241 Guemez-Gamboa, 2015, Inactivating mutations in MFSD2A, required for omega-3 fatty acid transport in brain, cause a lethal microcephaly syndrome, Nat. Genet., 47, 809, 10.1038/ng.3311 Harris, 2011, Twentieth-century trends in essential fatty acid intakes and the predicted omega-3 index: evidence versus estimates, Am. J. Clin. Nutr., 93, 907, 10.3945/ajcn.111.014365 Blasbalg, 2011, Changes in consumption of omega-3 and omega-6 fatty acids in the United States during the 20th century, Am. J. Clin. Nutr., 93, 950, 10.3945/ajcn.110.006643 Andriamampandry, 1999, Antithrombotic effects of (n−3) polyunsaturated fatty acids in rat models of arterial and venous thrombosis, Thromb. Res., 93, 9, 10.1016/S0049-3848(98)00149-2 Anil, 2007, The impact of EPA and DHA on blood lipids and lipoprotein metabolism: influence of apoE genotype, Proc. Nutr. Soc., 66, 9, 10.1017/S0029665107005307 Calder, 2002, Polyunsaturated fatty acids, inflammation and immunity, Eur. J. Clin. Nutr., 56, 6, 10.1038/sj.ejcn.1601478 Hooijmans, 2007, 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., 28, 16, 10.1016/j.nbd.2007.06.007 Oksman, 2006, Impact of different saturated fatty acid, polyunsaturated fatty acid and cholesterol containing diets on beta-amyloid accumulation in APP/PS1 transgenic mice, Neurobiol. Dis., 23, 563, 10.1016/j.nbd.2006.04.013 Simopoulos, 2006, Evolutionary aspects of diet, the omega-6/omega-3 ratio and genetic variation: nutritional implications for chronic diseases, Biomed Pharmacother, 60, 502, 10.1016/j.biopha.2006.07.080 Loef, 2013, The omega-6/omega-3 ratio and dementia or cognitive decline: a systematic review on human studies and biological evidence, J. Nutr. Gerontol. Geriatr., 32, 1, 10.1080/21551197.2012.752335 Neuringer, 1988, The essentiality of n−3 fatty acids for the development and function of the retina and brain, Annu. Rev. Nutr., 8, 25, 10.1146/annurev.nu.08.070188.002505 Carrié, 1999, Learning deficits in first generation OF1 mice deficient in (n−3) polyunsaturated fatty acids do not result from visual alteration, Neurosci. Lett., 266, 69, 10.1016/S0304-3940(99)00265-7 Weisinger, 1998, Effect of diet on the rate of depletion of n−3 fatty acids in the retina of the guinea pig, J. Lipid Res., 39, 1274, 10.1016/S0022-2275(20)32552-9 Arien, 2015, Omega-3 deficiency impairs honey bee learning, Proc. Natl. Acad. Sci. U. S. A., 112, 15761, 10.1073/pnas.1517375112 Igarashi, 2015, Impact of maternal n−3 polyunsaturated fatty acid deficiency on dendritic arbor morphology and connectivity of developing Xenopus laevis central neurons in vivo, J. Neurosci., 35, 6079, 10.1523/JNEUROSCI.4102-14.2015 Tinoco, 1978, Linolenic acid deficiency: changes in fatty acid patterns in female and male rats raised on a linolenic acid-deficient diet for two generations, Lipids, 13, 12, 10.1007/BF02533360 Ahmad, 2002, A decrease in cell size accompanies a loss of docosahexaenoate in the rat hippocampus, Nutr. Neurosci., 5, 103, 10.1080/10284150290018973 Cardoso, 2012, Differential vulnerability of substantia nigra and corpus striatum to oxidative insult induced by reduced dietary levels of essential fatty acids, Front. Hum. Neurosci., 10.3389/fnhum.2012.00249 Soares, 1995, Effect of essential fatty acid deficiency on membrane fatty acid content and growth hormone stimulation of rat pituitaries during postnatal development, J. Lipid Res., 36, 1401, 10.1016/S0022-2275(20)41147-2 Favrelière, 1998, Chronic dietary n−3 polyunsaturated fatty acids deficiency affects the fatty acid composition of plasmenylethanolamine and phosphatidylethanolamine differently in rat frontal cortex, striatum, and cerebellum, Lipids, 33, 401, 10.1007/s11745-998-0221-y Hichami, 2007, Olfactory discrimination ability and brain expression of c-fos, Gir and Glut1 mRNA are altered in n−3 fatty acid-depleted rats, Behav. Brain Res., 184, 1, 10.1016/j.bbr.2007.06.010 Foot, 1982, Influence of dietary fat on the lipid composition of rat brain synaptosomal and microsomal membranes, Biochem. J., 208, 631, 10.1042/bj2080631 Homayoun, 1988, Alteration in fatty acid composition of adult rat brain capillaries and choroid plexus induced by a diet deficient in n−3 fatty acids: slow recovery after substitution with a nondeficient diet, J. Neurochem., 51, 45, 10.1111/j.1471-4159.1988.tb04833.x Ahmad, 2002, Original article: decrease in neuron size in docosahexaenoic acid-deficient brain, Pediatr. Neurol., 26, 210, 10.1016/S0887-8994(01)00383-6 Passos, 2012, Dopaminergic cell populations of the rat substantia nigra are differentially affected by essential fatty acid dietary restriction over two generations, J. Chem. Neuroanat., 44, 66, 10.1016/j.jchemneu.2012.05.003 Ahmad, 2004, Gray and white matter brain volume in aged rats raised on n−3 fatty acid deficient diets, Nutr. Neurosci., 7, 13, 10.1080/1028415042000202009 de Velasco, 2012, Nutritional restriction of omega-3 fatty acids alters topographical fine tuning and leads to a delay in the critical period in the rodent visual system, Exp. Neurol., 234, 220, 10.1016/j.expneurol.2011.12.032 Innis, 2001, Dietary fatty acid composition in pregnancy alters neurite membrane fatty acids and dopamine in newborn rat brain, J. Nutr., 131, 10.1093/jn/131.1.118 Ikemoto, 2000, Dietary n−3 fatty acid deficiency decreases nerve growth factor content in rat hippocampus, Neurosci. Lett., 285, 99, 10.1016/S0304-3940(00)01035-1 Tsukada, 2000, Docosahexaenoic acid (DHA) improves the age-related impairment of the coupling mechanism between neuronal activation and functional cerebral blood flow response: a PET study in conscious monkeys, Brain Res., 862, 180, 10.1016/S0006-8993(00)02115-6 Wiesmann, 2016, A dietary treatment improves cerebral blood flow and brain connectivity in aging apoE4 mice, Neural Plast., 2016, 6846721, 10.1155/2016/6846721 Yamamoto, 1988, Effect of the dietary alpha-linolenate/linoleate balance on lipid compositions and learning ability of rats. II. Discrimination process, extinction process, and glycolipid compositions, J. Lipid Res., 29, 1013, 10.1016/S0022-2275(20)38463-7 Kodas, 2002, Reversibility of n−3 fatty acid deficiency-induced changes in dopaminergic neurotransmission in rats: critical role of developmental stage, J. Lipid Res., 43, 1209, 10.1194/jlr.M200132-JLR200 Weiser, 2015, Dietary DHA during development affects depression-like behaviors and biomarkers that emerge after puberty in adolescent rats, J. Lipid Res., 56, 10.1194/jlr.M055558 Velasco, 2012, Nutritional restriction of omega-3 fatty acids alters topographical fine tuning and leads to a delay in the critical period in the rodent visual system, Exp. Neurol., 234, 10.1016/j.expneurol.2011.12.032 Bondi, 2014, Adolescent behavior and dopamine availability are uniquely sensitive to dietary omega-3 fatty acid deficiency (English), Biol. Psychiatry, 75, 38, 10.1016/j.biopsych.2013.06.007 Levant, 2006, Sex-specific effects of brain LC-PUFA composition on locomotor activity in rats, Physiol. Behav., 89, 196, 10.1016/j.physbeh.2006.06.007 Levant, 2006, Reduced brain DHA content after a single reproductive cycle in female rats fed a diet deficient in N−3 polyunsaturated fatty acids, Biol. Psychiatry, 60, 987, 10.1016/j.biopsych.2005.12.013 Greiner, 1999, Rats with low levels of brain docosahexaenoic acid show impaired performance in olfactory-based and spatial learning tasks, Lipids, 34, 4, 10.1007/BF02562305 Martinez, 2001, Restoring the DHA levels in the brains of Zellweger patients, J. Mol. Neurosci., 16, 309, 10.1385/JMN:16:2-3:309 Goldfisher, 1973, Peroxisomal and mitochondrial defects in the cerebro-hepato-renal syndrome, Science, 182 Rahim, 2014, Central serotonergic neuron deficiency in a mouse model of Zellweger syndrome, Neuroscience, 274, 229, 10.1016/j.neuroscience.2014.05.034 Maxwell, 2003, Pex13 inactivation in the mouse disrupts peroxisome biogenesis and leads to a Zellweger syndrome phenotype, Mol. Cell. Biol., 23, 11, 10.1128/MCB.23.16.5947-5957.2003 Faust, 2001, The peroxisome deficient PEX2 Zellweger mouse, J. Mol. Neurosci., 16, 289, 10.1385/JMN:16:2-3:289 Crane, 2014, Revisiting the neuropathogenesis of Zellweger syndrome, Neurochem. Int., 69, 1, 10.1016/j.neuint.2014.02.007 Holman, 1982, A case of human linolenic acid deficiency involving neurological abnormalities, Am. J. Clin. Nutr., 35, 10.1093/ajcn/35.3.617 Meng, 1983, A case of human linolenic acid deficiency involving neurological abnormalities, Am. J. Clin. Nutr., 37, 157, 10.1093/ajcn/37.1.157 Francès, 1995, Effects of dietary alpha-linolenic acid deficiency on neuromuscular and cognitive functions in mice, Life Sci., 57, 1935, 10.1016/0024-3205(95)02180-Q Francès, 1996, Influence of a dietary α-linolenic acid deficiency on learning in the Morris water maze and on the effects of morphine, Eur. J. Pharmacol., 298, 217, 10.1016/0014-2999(95)00825-X Frances, 1996, Effect of dietary α-linolenic acid deficiency on habituation, Life Sci., 58, 1805, 10.1016/0024-3205(96)00164-6 Carrié, 2002, Docosahexaenoic acid-rich phospholipid supplementation: effect on behavior, learning ability, and retinal function in control and n−3 polyunsaturated fatty acid deficient old mice, Nutr. Neurosci., 5, 43, 10.1080/10284150290007074 Fedorova, 2009, An n−3 fatty acid deficiency impairs rat spatial learning in the Barnes maze, Behav. Neurosci., 123, 196, 10.1037/a0013801 Neuringer, 1986, Biochemical and functional effects of prenatal and postnatal omega 3 fatty acid deficiency on retina and brain in rhesus monkeys, Proc. Natl. Acad. Sci. U. S. A., 83, 10.1073/pnas.83.11.4021 Catalan, 2002, Cognitive deficits in docosahexaenoic acid-deficient rats, Behav. Neurosci., 116, 1022, 10.1037/0735-7044.116.6.1022 Grayson, 2014, Dietary omega-3 fatty acids modulate large-scale systems organization in the rhesus macaque brain, J. Neurosci., 34, 10.1523/JNEUROSCI.3038-13.2014 Francès, 2000, Nutritional (n−3) polyunsaturated fatty acids influence the behavioral responses to positive events in mice, Neurosci. Lett., 285, 223, 10.1016/S0304-3940(00)01065-X Delion, 1996, α-Linolenic acid dietary deficiency alters age-related changes of dopaminergic and serotoninergic neurotransmission in the rat frontal cortex, J. Neurochem., 66, 1582, 10.1046/j.1471-4159.1996.66041582.x McNamara, 2010, Omega-3 fatty acid deficiency increases constitutive pro-inflammatory cytokine production in rats: relationship with central serotonin turnover, Prostaglandins Leukot. Essent. Fatty Acids, 83, 185, 10.1016/j.plefa.2010.08.004 Latour, 2013, Omega-3 fatty acids deficiency aggravates glutamatergic synapse and astroglial aging in the rat hippocampal CA1, Aging Cell, 12, 76, 10.1111/acel.12026 Madore, 2014, Nutritional n−3 PUFAs deficiency during perinatal periods alters brain innate immune system and neuronal plasticity-associated genes, Brain Behav. Immun., 41, 22, 10.1016/j.bbi.2014.03.021 Borba, 2010, Essential fatty acid deficiency reduces cortical spreading depression propagation in rats: a two-generation study, Nutr. Neurosci., 13, 144, 10.1179/147683010X12611460763887 Harbeby, 2012, n−3 PUFA status affects expression of genes involved in neuroenergetics differently in the fronto-parietal cortex compared to the CA1 area of the hippocampus: effect of rest and neuronal activation in the rat, Prostaglandins Leukot. Essent. Fat. Acids, 86, 10, 10.1016/j.plefa.2012.04.008 Pifferi, 2005, (n−3) polyunsaturated fatty acid deficiency reduces the expression of both isoforms of the brain glucose transporter GLUT1 in rats, J. Nutr., 135, 2241, 10.1093/jn/135.9.2241 Ximenes da Silva, 2002, Glucose transport and utilization are altered in the brain of rats deficient in n−3 polyunsaturated fatty acids, J. Neurochem., 81, 1328, 10.1046/j.1471-4159.2002.00932.x Choeiri, 2005, Glucose transporter plasticity during memory processing, Neuroscience, 130, 591, 10.1016/j.neuroscience.2004.09.011 Larrieu, 2012, Nutritional n−3 polyunsaturated fatty acids deficiency alters cannabinoid receptor signaling pathway in the brain and associated anxiety-like behavior in mice, J. Physiol. Biochem., 68, 671, 10.1007/s13105-012-0179-6 Liu, 2013, Omega-3 polyunsaturated fatty acid (PUFA) status in major depressive disorder with comorbid anxiety disorders, J. Clin. Psychiatry, 74, 10.4088/JCP.12m07970 Palsdottir, 2012, Long-term effects of perinatal essential fatty acid deficiency on anxiety-related behavior in mice, Behav. Neurosci., 126, 361, 10.1037/a0027161 Ressler, 2000, Role of serotonergic and noradrenergic systems in the pathophysiology of depression and anxiety disorders, Depress. Anxiety, 12, 2, 10.1002/1520-6394(2000)12:1+<2::AID-DA2>3.0.CO;2-4 DeMar, 2006, One generation of n−3 polyunsaturated fatty acid deprivation increases depression and aggression test scores in rats, J. Lipid Res., 47, 172, 10.1194/jlr.M500362-JLR200 Carlezon, 2005, Antidepressant-like effects of uridine and omega-3 fatty acids are potentiated by combined treatment in rats, Biol. Psychiatry, 57, 10.1016/j.biopsych.2004.11.038 Huang, 2008, Omega-3 fatty acids on the forced-swimming test, J. Psychiatr. Res., 42, 10.1016/j.jpsychires.2006.09.004 Reisbick, 1994, Home cage behavior of rhesus monkeys with long-term deficiency of omega-3 fatty acids, Physiol. Behav., 55, 10.1016/0031-9384(94)90128-7 Conklin, 2007, Long-chain omega-3 fatty acid intake is associated positively with corticolimbic gray matter volume in healthy adults, Neurosci. Lett., 421, 10.1016/j.neulet.2007.04.086 Porsolt, 2001, Rodent models of depression: forced swimming and tail suspension behavioral despair tests in rats and mice Thomazeau, 2016, Nutritional n−3 PUFA deficiency abolishes endocannabinoid gating of hippocampal long-term potentiation, Cereb. Cortex, 10.1093/cercor/bhw052 Lafourcade, 2011, Nutritional omega-3 deficiency abolishes endocannabinoid-mediated neuronal functions, Nat. Neurosci., 14, 345, 10.1038/nn.2736 Yamada, 2016, Modulation of long-term potentiation of cortico-amygdala synaptic responses and auditory fear memory by dietary polyunsaturated fatty acid, Front. Behav. Neurosci., 10, 10.3389/fnbeh.2016.00164 Zimmer, 2000, Chronic n−3 polyunsaturated fatty acid deficiency alters dopamine vesicle density in the rat frontal cortex, Neurosci. Lett., 284, 25, 10.1016/S0304-3940(00)00950-2 Ahmad, 2008, Reduced numbers of dopamine neurons in the substantia nigra pars compacta and ventral tegmental area of rats fed an n−3 polyunsaturated fatty acid-deficient diet: a stereological study, Neurosci. Lett., 438, 303, 10.1016/j.neulet.2008.04.073 Kuperstein, 2008, Altered expression of key dopaminergic regulatory proteins in the postnatal brain following perinatal n−3 fatty acid dietary deficiency, J. Neurochem., 106, 662, 10.1111/j.1471-4159.2008.05418.x Zimmer, 2002, The dopamine mesocorticolimbic pathway is affected by deficiency in n−3 polyunsaturated fatty acids, Am. J. Clin. Nutr., 75, 662, 10.1093/ajcn/75.4.662 Kodas, 2002, Neither the density nor function of striatal dopamine transporters were influenced by chronic n−3 polyunsaturated fatty acid deficiency in rodents, Neurosci. Lett., 321, 95, 10.1016/S0304-3940(01)02481-8 Tang, 2016, Maternal diet of polyunsaturated fatty acid altered the cell proliferation in the dentate gyrus of hippocampus and influenced glutamatergic and serotoninergic systems of neonatal female rats, Lipids Health Dis., 15, 71, 10.1186/s12944-016-0236-1 Howes, 2011, Progressive increase in striatal dopamine synthesis capacity as patients develop psychosis: a PET study, Mol. Psychiatry, 16, 885, 10.1038/mp.2011.20 Bazinet, 2014, Polyunsaturated fatty acids and their metabolites in brain function and disease, Nat. Rev. Neurosci., 15, 771, 10.1038/nrn3820 Conway, 2014, Apolipoprotein E isoforms disrupt long-chain fatty acid distribution in the plasma, the liver and the adipose tissue of mice, Prostaglandins Leukot. Essent. Fatty Acids, 91, 261, 10.1016/j.plefa.2014.09.007 Arbones-Mainar, 2016, Metabolic shifts toward fatty-acid usage and increased thermogenesis are associated with impaired adipogenesis in mice expressing human APOE4, Int. J. Obes., 40, 1574, 10.1038/ijo.2016.93 Phillips, 2014, Apolipoprotein E isoforms and lipoprotein metabolism, IUBMB Life, 66, 616, 10.1002/iub.1314 Horrobin, 1981, Loss of delta-6-desaturase activity as a key factor in aging, Med. Hypotheses, 7, 1211, 10.1016/0306-9877(81)90064-5 Hostage, 2014, Mapping the effect of the apolipoprotein E genotype on 4-year atrophy rates in an Alzheimer disease-related brain network, Radiology, 271, 211, 10.1148/radiol.13131041 Bell, 2012, Apolipoprotein E controls cerebrovascular integrity via cyclophilin A, Nature, 485, 512, 10.1038/nature11087 Alata, 2015, Human apolipoprotein E varepsilon4 expression impairs cerebral vascularization and blood-brain barrier function in mice, J. Cereb. Blood Flow Metab., 35, 86, 10.1038/jcbfm.2014.172 Salloway, 2002, Effect of APOE genotype on microvascular basement membrane in Alzheimer's disease, J. Neurol. Sci., 203-204, 183, 10.1016/S0022-510X(02)00288-5 Halliday, 2016, Accelerated pericyte degeneration and blood-brain barrier breakdown in apolipoprotein E4 carriers with Alzheimer's disease, J. Cereb. Blood Flow Metab., 36, 216, 10.1038/jcbfm.2015.44 Knickmeyer, 2014, Common variants in psychiatric risk genes predict brain structure at birth, Cereb. Cortex, 24, 1230, 10.1093/cercor/bhs401 Dean, 2014, Brain differences in infants at differential genetic risk for late-onset Alzheimer disease: a cross-sectional imaging study, JAMA Neurol., 71, 11, 10.1001/jamaneurol.2013.4544 Shaw, 2007, Cortical morphology in children and adolescents with different apolipoprotein E gene polymorphisms: an observational study, Lancet Neurol., 6, 494, 10.1016/S1474-4422(07)70106-0 Salvato, 2015, Does apolipoprotein E genotype influence cognition in middle-aged individuals?, Curr. Opin. Neurol., 28, 612, 10.1097/WCO.0000000000000262 Sheline, 2010, APOE4 allele disrupts resting state fMRI connectivity in the absence of amyloid plaques or decreased CSF Aβ42, J. Neurosci., 30, 17035, 10.1523/JNEUROSCI.3987-10.2010 Adamson, 2010, Apolipoprotein E ɛ4 influences on episodic recall and brain structures in aging pilots, Neurobiol. Aging, 31, 1059, 10.1016/j.neurobiolaging.2008.07.017 Kozauer, 2008, Apolipoprotein E genotype and lifetime cognitive decline, Int. Psychogeriatr., 20, 109, 10.1017/S104161020700587X Wilson, 2011, Vulnerability to stress, anxiety, and development of dementia in old age, Am. J. Geriatr. Psychiatry, 19, 327, 10.1097/JGP.0b013e31820119da Greenwood, 2014, Longitudinal change in working memory as a function of APOE genotype in midlife and old age, Scand. J. Psychol., 55, 268, 10.1111/sjop.12123 Greenwood, 2000, Genetics and visual attention: selective deficits in healthy adult carriers of the ɛ4 allele of the apolipoprotein E gene, Proc. Natl. Acad. Sci., 97, 11661, 10.1073/pnas.97.21.11661 Greenwood, 2005, Effects of apolipoprotein E genotype on spatial attention, working memory, and their interaction in healthy, middle-aged adults: results from the National Institute of Mental Health's BIOCARD study, Neuropsychology, 19, 199, 10.1037/0894-4105.19.2.199 Zipser, 2007, Microvascular injury and blood-brain barrier leakage in Alzheimer's disease, Neurobiol. Aging, 28, 977, 10.1016/j.neurobiolaging.2006.05.016 Suri, 2014, Reduced cerebrovascular reactivity in young adults carrying the APOE epsilon4 allele, Alzheimers Dement. Lin, 2015, Docosahexaenoic acid attenuates hyperglycemia-enhanced hemorrhagic transformation after transient focal cerebral ischemia in rats, Neuroscience, 301, 471, 10.1016/j.neuroscience.2015.06.024 Andreone, 2017, Blood-brain barrier permeability is regulated by lipid transport-dependent suppression of caveolae-mediated transcytosis, Neuron, 94, 10.1016/j.neuron.2017.03.043 Abdullah, 2016, APOE4 specific imbalance in arachidonic acid and docosahexaenoic acid in serum phospholipids from individuals with preclinical MCI/AD Abdullah, 2016, APOE4 genotype dependent deficits in DHA containing phospholipids and DHA transporters in the cerebrovasculature of Alzheimer's disease patients Chouinard-Watkins, 2017, Docosahexaenoic acid prevents cognitive deficits in human apolipoprotein E epsilon 4-targeted replacement mice, Neurobiol. Aging, 57, 28, 10.1016/j.neurobiolaging.2017.05.003 Yijun, 2015, The impact of docosahexaenoic acid on Alzheimer's disease: is there a role of the blood-brain barrier?, Curr. Clin. Pharmacol., 10, 222, 10.2174/157488471003150820151532 Mahley, 1988, Apolipoprotein E: cholesterol transport protein with expanding role in cell biology, Science, 240, 622, 10.1126/science.3283935 Pitas, 1987, Astrocytes synthesize apolipoprotein E and metabolize apolipoprotein E-containing lipoproteins, Biochim. Biophys. Acta, 917, 148, 10.1016/0005-2760(87)90295-5 Vandal, 2014, Reduction in DHA transport to the brain of mice expressing human APOE4 compared to APOE2, J. Neurochem., 129, 516, 10.1111/jnc.12640 Chouinard-Watkins, 2013, Disturbance in uniformly 13C-labelled DHA metabolism in elderly human subjects carrying the apoE epsilon4 allele, Br. J. Nutr., 110, 1751, 10.1017/S0007114513001268 Yassine, 2017, Association of docosahexaenoic acid supplementation with Alzheimer disease stage in apolipoprotein E epsilon4 carriers: a review, JAMA Neurol., 10.1001/jamaneurol.2016.4899 Yassine, 2016, Association of serum docosahexaenoic acid with cerebral amyloidosis, JAMA Neurol., 73, 1208, 10.1001/jamaneurol.2016.1924 Anderson, 2005, Can prenatal N−3 fatty acid deficiency be completely reversed after birth? Effects on retinal and brain biochemistry and visual function in rhesus monkeys, Pediatr. Res., 58, 10.1203/01.pdr.0000182188.31596.5a Connor, 1990, Dietary effects on brain fatty acid composition: the reversibility of n−3 fatty acid deficiency and turnover of docosahexaenoic acid in the brain, erythrocytes, and plasma of rhesus monkeys, J. Lipid Res., 31, 237, 10.1016/S0022-2275(20)43209-2 Chen, 2013, Exposure to a maternal n−3 fatty acid-deficient diet during brain development provokes excessive hypothalamic-pituitary-adrenal axis responses to stress and behavioral indices of depression and anxiety in male rat offspring later in life, J. Nutr. Biochem., 24, 10.1016/j.jnutbio.2012.02.006 Moriguchi, 2001, Reversal of docosahexaenoic acid deficiency in the rat brain, retina, liver, and serum, J. Lipid Res., 42, 419, 10.1016/S0022-2275(20)31666-7 Tanaka, 2007, Early dietary treatments with Lorenzo's oil and docosahexaenoic acid for neurological development in a case with Zellweger syndrome, Brain Dev., 29, 586, 10.1016/j.braindev.2007.02.005 Chen, 2012, Fish oil supplementation of maternal rats on an n−3 fatty acid-deficient diet prevents depletion of maternal brain regional docosahexaenoic acid levels and has a postpartum anxiolytic effect, J. Nutr. Biochem., 23, 299, 10.1016/j.jnutbio.2010.12.010 Carrié, 2000, Phospholipid supplementation reverses behavioral and biochemical alterations induced by n–3 polyunsaturated fatty acid deficiency in mice, J. Lipid Res., 41, 473, 10.1016/S0022-2275(20)34486-2 Paker, 2010, Docosahexaenoic acid therapy in peroxisomal diseases: results of a double-blind, randomized trial, Neurology, 75, 5, 10.1212/WNL.0b013e3181f07061 Martinez, 1996, Docosahexaenoic acid therapy in docosahexaenoic acid-deficient patients with disorders of peroxisomal biogenesis, Lipids, 31, 8, 10.1007/BF02637067 Martínez, 1999, Treatment of generalized peroxisomal disorders with docosahexaenoic acid ethyl ether, Rev. Neurol., 28, 6 Kodas, 2004, Serotoninergic neurotransmission is affected by n−3 polyunsaturated fatty acids in the rat, J. Neurochem., 89, 695, 10.1111/j.1471-4159.2004.02401.x Freund Levi, 2014, Transfer of omega-3 fatty acids across the blood–brain barrier after dietary supplementation with a docosahexaenoic acid-rich omega-3 fatty acid preparation in patients with Alzheimer's disease: the OmegAD study, J. Intern. Med., 275, 428, 10.1111/joim.12166 Hjorth, 2013, Omega-3 fatty acids enhance phagocytosis of Alzheimer's disease-related amyloid-42 by human microglia and decrease inflammatory markers, J. Alzheimers Dis., 35, 17, 10.3233/JAD-130131 Rosell, 2005, Long-chain n–3 polyunsaturated fatty acids in plasma in British meat-eating, vegetarian, and vegan men, Am. J. Clin. Nutr., 82, 327, 10.1093/ajcn/82.2.327 Kornsteiner, 2008, Very low n–3 long-chain polyunsaturated fatty acid status in Austrian vegetarians and vegans, Ann. Nutr. Metab., 52, 37, 10.1159/000118629 Rapoport, 2009, Can the rat liver maintain normal brain DHA metabolism in the absence of dietary DHA?, Prostaglandins Leukot. Essent. Fatty Acids, 81, 10.1016/j.plefa.2009.05.021 Igarashi, 2007, Dietary n−3 PUFA deprivation for 15weeks upregulates elongase and desaturase expression in rat liver but not brain, J. Lipid Res., 48, 2463, 10.1194/jlr.M700315-JLR200 Cunnane, 2013, Docosahexaenoic acid homeostasis, brain aging and Alzheimer's disease: can we reconcile the evidence?, Prostaglandins Leukot. Essent. Fatty Acids, 88, 61, 10.1016/j.plefa.2012.04.006 Cunnane, 2012, Plasma and brain fatty acid profiles in mild cognitive impairment and Alzheimer's disease, J. Alzheimers Dis., 29, 691, 10.3233/JAD-2012-110629 Domenichiello, 2017, Whole-body docosahexaenoic acid synthesis-secretion rates in rats are constant across a large range of dietary α-linolenic acid intakes, J. Nutr., 147, 37, 10.3945/jn.116.232074 Welch, 2010, Am. J. Clin. Nutr., 92, 1040, 10.3945/ajcn.2010.29457 Wang, 2015, Recent insights into the biological functions of liver fatty acid binding protein 1, J. Lipid Res., 56, 2238, 10.1194/jlr.R056705 Chouinard-Watkins, 2016, A diet rich in docosahexaenoic acid restores liver arachidonic acid and docosahexaenoic acid concentrations in mice homozygous for the human apolipoprotein E ε4 allele, J. Nutr., 146, 1315, 10.3945/jn.116.230052 Zhang, 2017, Fatty acid transporting proteins: roles in brain development, aging, and stroke, Prostaglandins Leukot. Essent. Fat. Acids Cunnane, 2016, Can ketones compensate for deteriorating brain glucose uptake during aging? Implications for the risk and treatment of Alzheimer's disease, Ann. N. Y. Acad. Sci., 1367, 12, 10.1111/nyas.12999 Pincon, 2016, Human apolipoprotein E allele and docosahexaenoic acid intake modulate peripheral cholesterol homeostasis in mice, J. Nutr. Biochem., 34, 83, 10.1016/j.jnutbio.2016.05.001 Hennebelle, 2014, Ageing and apoE change DHA homeostasis: relevance to age-related cognitive decline, Proc. Nutr. Soc., 73, 7, 10.1017/S0029665113003625 Chouinard-Watkins, 2015, Interactive impact of BMI and APOE genotype on the plasma long chain polyunsaturated fatty acid response to a fish oil supplement in healthy participants, Am. J. Clin. Nutr., 102, 505, 10.3945/ajcn.114.103507 Chen, 2015, Plasma non-esterified docosahexaenoic acid is the major pool supplying the brain, Sci Rep, 5, 15791, 10.1038/srep15791