Role of docosahexaenoic acid in the modulation of glial cells in Alzheimer's disease

Journal of Neuroinflammation

Volumn 13, Issue 1, 2016, Pages

  Heras Sandoval, David ^a,b   Pedraza Chaverri, José ^a   Pérez Rojas, Jazmin M ^b  

^a Universidad Nacional Autonoma de Mexico Facultad de Quimica   (Mexico)

^b INSTITUTO NACIONAL DE CANCEROLOGÍA   (Mexico)

Author keywords

Alzheimer's disease (AD); Amyloid peptide (A ); Docosahexaenoic acid (DHA); Glial cells; Neuroinflammation; Neuroprotectin D1 (NPD1); Resolvin D1 (RvD1)

Indexed keywords

DOCOSAHEXAENOIC ACID; INTERLEUKIN 1; INTERLEUKIN 12; INTERLEUKIN 18; INTERLEUKIN 1BETA; INTERLEUKIN 6; MITOGEN ACTIVATED PROTEIN KINASE P38; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR GAMMA; RETINOID X RECEPTOR; TRANSFORMING GROWTH FACTOR BETA; TUMOR NECROSIS FACTOR ALPHA; AMYLOID BETA PROTEIN;

ALZHEIMER DISEASE; ASTROCYTE; BLOOD BRAIN BARRIER; CELL DIFFERENTIATION; CELL INFILTRATION; CYTOKINE PRODUCTION; DIMERIZATION; FATTY ACID ANALYSIS; GLIA CELL; GLUTAMATERGIC SYNAPSE; HUMAN; HYDROLYSIS; IMMUNOPHENOTYPING; LEUKOCYTE; LIPID METABOLISM; MICROGLIA; NERVOUS SYSTEM INFLAMMATION; NEUROMODULATION; NEUROPROTECTION; NEUROTRANSMISSION; NONHUMAN; OXYGENATION; PIGMENT EPITHELIUM; PROTEIN DEGRADATION; REVIEW; SYNAPTIC MEMBRANE; SYNAPTIC TRANSMISSION; ANIMAL; DRUG EFFECTS; GENETICS; GLIA; METABOLISM; PATHOLOGY;

ALZHEIMER DISEASE; AMYLOID BETA-PEPTIDES; ANIMALS; DOCOSAHEXAENOIC ACIDS; HUMANS; NEUROGLIA; PPAR GAMMA;

EID: 84960467663     PISSN: None     EISSN: 17422094     Source Type: Journal    
DOI: 10.1186/s12974-016-0525-7     Document Type: Review

References (132)

1. Calder PC. Mechanisms of action of (n-3) fatty acids. J Nutr. 2012;142:592S-9.
2. SanGiovanni JP, Chew EY. The role of omega-3 long-chain polyunsaturated fatty acids in health and disease of the retina. Prog Retin Eye Res. 2005;24:87-138.
3. Pereira H, Barreira L, Figueiredo F, Custódio L, Vizetto-Duarte C, Polo C, et al. Polyunsaturated fatty acids of marine macroalgae: potential for nutritional and pharmaceutical applications. Mar Drugs. 2012;10:1920-35.
4. Williams CM, Burdge G. Long-chain n-3 PUFA: plant v. marine sources. Proc Nutr Soc. 2006;65:42-50.
5. Morse NL. Benefits of docosahexaenoic acid, folic acid, vitamin D and iodine on foetal and infant brain development and function following maternal supplementation during pregnancy and lactation. Nutrients. 2012;4:799-840.
6. Carlson SE. Docosahexaenoic acid and arachidonic acid in infant development. Semin Neonatol. 2001;6:437-49.
7. Burri L, Hoem N, Banni S, Berge K. Marine omega-3 phospholipids: metabolism and biological activities. Int J Mol Sci. 2012;13:15401-19.
8. Kihara A. Very long-chain fatty acids: elongation, physiology and related disorders. J Biochem. 2012;152:387-95.
9. Sprecher H, Luthria DL, Mohammed BS, Baykousheva SP. Reevaluation of the pathways for the biosynthesis of polyunsaturated fatty acids. J Lipid Res. 1995;36:2471-7.
10. Huffman SL, Harika RK, Eilander A, Osendarp SJ. Essential fats: how do they affect growth and development of infants and young children in developing countries? A literature review. Matern Child Nutr. 2011;Suppl 3:44-65.
11. Arterburn LM, Hall EB, Oken H. Distribution, interconversion, and dose response of n-3 fatty acids in humans. Am J Clin Nutr. 2006;83:1467S-76.
12. Rapoport SI, Rao JS, Igarashi M. Brain metabolism of nutritionally essential polyunsaturated fatty acids depends on both the diet and the liver. Prostaglandins Leukot Essent Fatty Acids. 2007;77:251-61.
13. 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;81:119-23.
14. Gibson RA, Neumann MA, Lien EL, Boyd KA, Tu WC. Docosahexaenoic acid synthesis from alpha-linolenic acid is inhibited by diets high in polyunsaturated fatty acids. Prostaglandins Leukot Essent Fatty Acids. 2013;88:139-46.
15. Bazan NG. Neuroprotectin D1-mediated anti-inflammatory and survival signaling in stroke, retinal degenerations, and Alzheimer's disease. J Lipid Res. 2009;50 Suppl:S400-5.
16. Lauritzen L, Hansen HS, Jørgensen MH, Michaelsen KF. The essentiality of long chain n-3 fatty acids in relation to development and function of the brain and retina. Prog Lipid Res. 2001;40:1-94.
17. Rapoport SI, Ramadan E, Basselin M. Docosahexaenoic acid (DHA) incorporation into the brain from plasma as an in vivo biomarker of brain DHA metabolism and neurotransmission. Prostaglandins Other Lipid Mediat. 2011;96:109-13.
18. Glomset JA. Role of docosahexaenoic acid in neuronal plasma membranes. Sci STKE. 2006;2006:pe6.
19. Guesnet P, Alessandri JM. Docosahexaenoic acid (DHA) and the developing central nervous system (CNS)-implications for dietary recommendations. Biochimie. 2011;93:7-12.
20. Guest J, Garg M, Bilgin A, Grant R. Relationship between central and peripheral fatty acids in humans. Lipids Health Dis. 2013;2:79.
21. Ouellet M, Emond V, Chen CT, Julien C, Bourasset F, Oddo S, et al. Diffusion of docosahexaenoic and eicosapentaenoic acids through the blood-brain barrier: an in situ cerebral perfusion study. Neurochem Int. 2009;55:476-82.
22. Brossard N, Croset M, Normand S, Pousin J, Lecerf J, Laville M, et al. Human plasma albumin transports [13C] docosahexaenoic acid in two lipid forms to blood cells. J Lipid Res. 1997;38:1571-82.
23. Mitchell RW, On NH, Del Bigio MR, Miller DW, Hatch GM. Fatty acid transport protein expression in human brain and potential role in fatty acid transport across human brain microvessel endothelial cells. J Neurochem. 2011;117:735-46.
24. Ma D, Zhang M, Mori Y, Yao C, Larsen CP, Yamashima T, et al. Cellular localization of epidermal-type and brain-type fatty acid-binding proteins in adult hippocampus and their response to cerebral ischemia. Hippocampus. 2010;20:811-9.
25. Nguyen LN, Ma D, Shui G, Wong P, Cazenave-Gassiot A, Zhang X, et al. Mfsd2a is a transporter for the essential omega-3 fatty acid docosahexaenoic acid. Nature. 2014;509:503-6.
26. Thies F, Pillon C, Moliere P, Lagarde M, Lecerf J. Preferential incorporation of sn-2 lysoPC DHA over unesterified DHA in the young rat brain. Am J Physiol. 1994;267:R1273-9.
27. Chen S, Subbaiah PV. Regioisomers of phosphatidylcholine containing DHA and their potential to deliver DHA to the brain: role of phospholipase specificities. Lipids. 2013;48:675-86.
28. Moore SA, Yoder E, Murphy S, Dutton GR, Spector AA. Astrocytes, not neurons, produce docosahexaenoic acid (22:6 omega-3) and arachidonic acid (20:4 omega-6). J Neurochem. 1991;56:518-24.
29. Williard DE, Harmon SD, Kaduce TL, Preuss M, Moore SA, Robbins ME, et al. Docosahexaenoic acid synthesis from n-3 polyunsaturated fatty acids in differentiated rat brain astrocytes. J Lipid Res. 2001;42:1368-76.
30. Moore SA. Polyunsaturated fatty acid synthesis and release by brain-derived cells in vitro. J Mol Neurosci. 2001;16(2-3):195-200.
31. Bazan NG. Cellular and molecular events mediated by docosahexaenoic acid-derived neuroprotectin D1 signaling in photoreceptor cell survival and brain protection. Prostaglandins Leukot Essent Fatty Acids. 2009;81:205-11.
32. Tu WC, Cook-Johnson RJ, James MJ, Mühlhäusler BS, Stone DA, Gibson RA. Barramundi (Lates calcarifer) desaturase with 6/8 dual activities. Biotechnol Lett. 2012;34:1283-96.
33. Kim HY, Akbar M, Kim YS. Phosphatidylserine-dependent neuroprotective signaling promoted by docosahexaenoic acid. Prostaglandins Leukot Essent Fatty Acids. 2010;82:165-72.
34. Cao D, Kevala K, Kim J, Moon HS, Jun SB, Lovinger D, et al. Docosahexaenoic acid promotes hippocampal neuronal development and synaptic function. J Neurochem. 2009;111:510-21.
35. Hong S, Lu Y, Yang R, Gotlinger KH, Petasis NA, Serhan CN. Resolvin D1, protectin D1, and related docosahexaenoic acid-derived products: analysis via electrospray/low energy tandem mass spectrometry based on spectra and fragmentation mechanisms. J Am Soc Mass Spectrom. 2007;18:128-44.
36. Ariel A, Li PL, Wang W, Tang WX, Fredman G, Hong S, et al. The docosatriene protectin D1 is produced by TH2 skewing and promotes human T cell apoptosis via lipid raft clustering. J Biol Chem. 2005;280:43079-86.
37. Zhao Y, Calon F, Julien C, Winkler JW, Petasis NA, Lukiw WJ, et al. Docosahexaenoic acid-derived neuroprotectin D1 induces neuronal survival via secretase- and PPARγ-mediated mechanisms in Alzheimer's disease models. PLoS One. 2011;6:e15816.
38. Bordoni A, Di Nunzio M, Danesi F, Biagi PL. Polyunsaturated fatty acids: from diet to binding to PPARs and other nuclear receptors. Genes Nutr. 2006;1:95-106.
39. Picq M, Chen P, Perez M, Michaud M, Véricel E, Guichardant M, et al. DHA metabolism: targeting the brain and lipoxygenation. Mol Neurobiol. 2010;42:48-51.
40. Chen P, Véricel E, Lagarde M, Guichardant M. Poxytrins, a class of oxygenated products from polyunsaturated fatty acids, potently inhibit blood platelet aggregation. FASEB J. 2011;25:382-8.
41. Serhan CN, Hong S, Gronert K, Colgan SP, Devchand PR, Mirick G, et al. Resolvins: a family of bioactive products of omega-3 fatty acid transformation circuits initiated by aspirin treatment that counter proinflammation signals. J Exp Med. 2002;196:1025-37.
42. Dalli J, Colas RA, Serhan CN. Novel n-3 immunoresolvents: structures and actions. Sci Rep. 2013;3:1940.
43. Dyall SC, Michael GJ, Michael-Titus AT. Omega-3 fatty acids reverse age-related decreases in nuclear receptors and increase neurogenesis in old rats. J Neurosci Res. 2010;88:2091-102.
44. Itoh T, Yamamoto K. Peroxisome proliferator activated receptor gamma and oxidized docosahexaenoic acids as new class of ligand. Naunyn Schmiedebergs Arch Pharmacol. 2008;377:541-7.
45. Cimini A, Benedetti E, Cristiano L, Sebastiani P, D'Amico MA, D'Angelo B, et al. Expression of peroxisome proliferator-activated receptors (PPARs) and retinoic acid receptors (RXRs) in rat cortical neurons. Neuroscience. 2005;130:325-37.
46. Cristiano L, Cimini A, Moreno S, Ragnelli AM, Paola CM. Peroxisome proliferator-activated receptors (PPARs) and related transcription factors in differentiating astrocyte cultures. Neuroscience. 2005;131:577-87.
47. Aleshin S, Grabeklis S, Hanck T, Sergeeva M, Reiser G. Peroxisome proliferator-activated receptor (PPAR)-gamma positively controls and PPARalpha negatively controls cyclooxygenase-2 expression in rat brain astrocytes through a convergence on PPARbeta/delta via mutual control of PPAR expression levels. Mol Pharmacol. 2009;76:414-24.
48. Holtzman DM, Morris JC, Goate AM. Alzheimer's disease: the challenge of the second century. Sci Transl Med. 2011;3:77sr1.
49. Blennow K, de Leon MJ, Zetterberg H. Alzheimer's disease. Lancet. 2006;368:387-403.
50. Heppner FL, Ransohoff RM, Becher B. Immune attack: the role of inflammation in Alzheimer disease. Nat Rev Neurosci. 2015;16:358-72.
51. Lucin KM, Wyss-Coray T. Immune activation in brain aging and neurodegeneration: too much or too little? Neuron. 2009;64:110-22.
52. Farfara D, Lifshitz V, Frenkel D. Neuroprotective and neurotoxic properties of glial cells in the pathogenesis of Alzheimer's disease. J Cell Mol Med. 2008;12:762-80.
53. Weitz TM, Town T. Microglia in Alzheimer's disease: it's all about context. Int J Alzheimers Dis. 2012;2012:314185.
54. Lee KM, MacLean AG. New advances on glial activation in health and disease. World J Virol. 2015;4:42-55.
55. Rossi D. Astrocyte physiopathology: at the crossroads of intercellular networking, inflammation and cell death. Prog Neurobiol. 2015;130:86-120.
56. Avila-Muñoz E, Arias C. When astrocytes become harmful: functional and inflammatory responses that contribute to Alzheimer's disease. Ageing Res Rev. 2014;18:29-40.
57. Heneka MT, Carson MJ, El Khoury J, Landreth GE, Brosseron F, Feinstein DL, et al. Neuroinflammation in Alzheimer's disease. Lancet Neurol. 2015;14:388-405.
58. Lian H, Yang L, Cole A, Sun L, Chiang AC, Fowler SW, et al. NFΚB-activated astroglial release of complement C3 compromises neuronal morphology and function associated with Alzheimer's disease. Neuron. 2015;85:101-15.
59. Woodruff TM, Tenner AJ. A commentary on: NFΚB-activated astroglial release of complement C3 compromises neuronal morphology and function associated with Alzheimer's disease. A cautionary note regarding C3aR. Front Immunol. 2015;6:220.
60. Meyer-Luehmann M, Spires-Jones TL, Prada C, Garcia-Alloza M, de Calignon A, Rozkalne A, et al. Rapid appearance and local toxicity of amyloid-beta plaques in a mouse model of Alzheimer's disease. Nature. 2008;451:720-4.
61. Marlatt MW, Bauer J, Aronica E, van Haastert ES, Hoozemans JJ, Joels M, et al. Proliferation in the Alzheimer hippocampus is due to microglia, not astroglia, and occurs at sites of amyloid deposition. Neural Plast. 2014;2014:693851.
62. Rodríguez JJ, Noristanic HN, Hilditchd T, Olabarriad M, Yehd CY, Wittone J, et al. Increased densities of resting and activated microglia in the dentate gyrus follow senile plaque formation in the CA1 subfield of the hippocampus in the triple transgenic model of Alzheimer's disease. Neurosci Lett. 2013;552:129-34.
63. Mulder SD, Nielsen HM, Blankenstein MA, Eikelenboom P, Veerhuis R. Apolipoproteins E and J interfere with amyloid-beta uptake by primary human astrocytes and microglia in vitro. Glia. 2014;62:493-503.
64. Li L, Wu Y, Wang Y, Wu J, Song L, Xian W, et al. Resolvin D1 promotes the interleukin-4-induced alternative activation in BV-2 microglial cells. J Neuroinflammation. 2014;11:72.
65. Xu J, Storer PD, Chavis JA, Racke MK, Drew PD. Agonists for the peroxisome proliferator-activated receptor-alpha and the retinoid X receptor inhibit inflammatory responses of microglia. J Neurosci Res. 2005;81:403-11.
66. Manzhulo IV, Ogurtsova OS, Lamash NE, Latyshev NA, Kasyanov SP, Dyuizen IV. Analgetic effect of docosahexaenoic acid is mediated by modulating the microglia activity in the dorsal root ganglia in a rat model of neuropathic pain. Acta Histochem. 2015;117:659-66.
67. Lu Y, Zhao LX, Cao DL, Gao YJ. Spinal injection of docosahexaenoic acid attenuates carrageenan-induced inflammatory pain through inhibition of microglia-mediated neuroinflammation in the spinal cord. Neuroscience. 2013;241:22-31.
68. Chen S, Zhang H, Pu H, Wang G, Li W, Leak RK, et al. n-3 PUFA supplementation benefits microglial responses to myelin pathology. Sci Rep. 2014;4:7458.
69. Pettit LK, Varsanyi C, Tadros J, Vassiliou E. Modulating the inflammatory properties of activated microglia with docosahexaenoic acid and aspirin. Lipids Health Dis. 2013;12:16.
70. De Smedt-Peyrusse V, Sargueil F, Moranis A, Harizi H, Mongrand S, Layé S. Docosahexaenoic acid prevents lipopolysaccharide-induced cytokine production in microglial cells by inhibiting lipopolysaccharide receptor presentation but not its membrane subdomain localization. J Neurochem. 2008;105:296-307.
71. Antonietta Ajmone-Cat M, Lavinia Salvatori M, De Simone R, Mancini M, Biagioni S, Bernardo A, et al. Docosahexaenoic acid modulates inflammatory and antineurogenic functions of activated microglial cells. J Neurosci Res. 2012;90:575-87.
72. Farese RV, Walther TC. Lipid droplets finally get a little R-E-S-P-E-C-T. Cell. 2009;139:855-60.
73. Saka HA, Valdivia R. Emerging roles for lipid droplets in immunity and host-pathogen interactions. Annu Rev Cell Dev Biol. 2012;28:411-37.
74. 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.
75. Mirza M, Volz C, Karlstetter M, Langiu M, Somogyi A, Ruonala MO, et al. Progressive retinal degeneration and glial activation in the CLN6 (nclf) mouse model of neuronal ceroid lipofuscinosis: a beneficial effect of DHA and curcumin supplementation. PLoS One. 2013;8:e75963.
76. Hjorth E, Zhu M, Toro VC, Vedin I, Palmblad J, Cederholm T, et al. Omega-3 fatty acids enhance phagocytosis of Alzheimer's disease-related amyloid-β42 by human microglia and decrease inflammatory markers. J Alzheimers Dis. 2013;35:697-713.
77. Lu DY, Tsao YY, Leung YM, Su KP. Docosahexaenoic acid suppresses neuroinflammatory responses and induces heme oxygenase-1 expression in BV-2 microglia: implications of antidepressant effects for ω-3 fatty acids. Neuropsychopharmacology. 2010;35:2238-48.
78. Ebert S, Weigelt K, Walczak Y, Drobnik W, Mauerer R, Hume DA, et al. Docosahexaenoic acid attenuates microglial activation and delays early retinal degeneration. Neurochem. 2009;110:1863-75.
79. Chang CY, Kuan YH, Li JR, Chen WY, Ou YC, Pan HC, et al. Docosahexaenoic acid reduces cellular inflammatory response following permanent focal cerebral ischemia in rats. J Nutr Biochem. 2013;24:2127-37.
80. Hjorth E, Freund-Levi Y. Immunomodulation of microglia by docosahexaenoic acid and eicosapentaenoic acid. Curr Opin Clin Nutr Metab Care. 2012;15:134-43.
81. Becerir C, Kili ç I, Sahin Ö, Özdemir Ö, Tokgün O, Özdemir B, et al. The protective effect of docosahexaenoic acid on the bilirubin neurotoxicity. J Enzyme Inhib Med Chem. 2013;28:801-7.
82. Gupta S, Knight AG, Gupta S, Keller JN, Bruce-Keller AJ. Saturated long-chain fatty acids activate inflammatory signaling in astrocytes. J Neurochem. 2012;120:1060-71.
83. Begum G, Kintner D, Liu Y, Cramer SW, Sun D. DHA inhibits ER Ca2+ release and ER stress in astrocytes following in vitro ischemia. J Neurochem. 2012;120:622-30.
84. Grintal B, Champeil-Potokar G, Lavialle M, Vancassel S, Breton S, Denis I. Inhibition of astroglial glutamate transport by polyunsaturated fatty acids: evidence for a signalling role of docosahexaenoic acid. Neurochem Int. 2009;54:535-43.
85. Latour A, Grintal B, Champeil-Potokar G, Hennebelle M, Lavialle M, Dutar P, et al. Omega-3 fatty acids deficiency aggravates glutamatergic synapse and astroglial aging in the rat hippocampal CA1. Aging Cell. 2013;12:76-84.
86. Sheets KG, Jun B, Zhou Y, Zhu M, Petasis NA, Gordon WC, et al. Microglial ramification and redistribution concomitant with the attenuation of choroidal neovascularization by neuroprotectin D1. Mol Vis. 2013;19:1747-59.
87. Abdelmoaty S, Wigerblad G, Bas DB, Codeluppi S, Fernandez-Zafra T, El-Awady e-S, et al. Spinal actions of lipoxin A4 and 17(R)-resolvin D1 attenuate inflammation-induced mechanical hypersensitivity and spinal TNF release. PLoS One. 2013;8:e75543.
88. Mizwicki MT, Liu G, Fiala M, Magpantay L, Sayre J, Siani A, et al. 1α, 25-dihydroxyvitamin D3 and resolvin D1 retune the balance between amyloid-β phagocytosis and inflammation in Alzheimer's disease patients. J Alzheimers Dis. 2013;34:155-70.
89. Yamanaka M, Ishikawa T, Griep A, Axt D, Kummer MP, Heneka MT. PPARγ/RXRα-induced and CD36-mediated microglial amyloid-β phagocytosis results in cognitive improvement in amyloid precursor protein/presenilin 1 mice. J Neurosci. 2012;32:17321-31.
90. Bahety P, Tan YM, Hong Y, Zhang L, Chan EC, Ee PL. Metabotyping of docosahexaenoic acid-treated Alzheimer's disease cell model. PLoS One. 2014;9:e90123.
91. Seo J, Barhoumi R, Johnson AE, Lupton JR, Chapkin RS. Docosahexaenoic acid selectively inhibits plasma membrane targeting of lipidated proteins. FASEB J. 2006;20:770-2.
92. Raza Shaikh S, Brown DA. Models of plasma membrane organization can be applied to mitochondrial membranes to target human health and disease with polyunsaturated fatty acids. Prostaglandins Leukot Essent Fatty Acids. 2013;88:21-5.
93. Grimm MO, Kuchenbecker J, Grösgen S, Burg VK, Hundsdörfer B, Rothhaar TL, et al. Docosahexaenoic acid reduces amyloid beta production via multiple pleiotropic mechanisms. J Biol Chem. 2011;286:14028-39.
94. Fabelo N, Martín V, Marín R, Moreno D, Ferrer I, Díaz M. Altered lipid composition in cortical lipid rafts occurs at early stages of sporadic Alzheimer's disease and facilitates APP/BACE1 interactions. Neurobiol Aging. 2014;35:1801-12.
95. Oksman M, Iivonen H, Hogyes E, Amtul Z, Penke B, Leenders I, et al. Impact of different saturated fatty acid, polyunsaturated fatty acid and cholesterol containing diets on beta-amyloid accumulation in APP/PS1 transgenic mice. Neurobiol Dis. 2006;23:563-72.
96. Eckert GP, Chang S, Eckmann J, Copanaki E, Hagl S, Hener U, et al. Liposome-incorporated DHA increases neuronal survival by enhancing non-amyloidogenic APP processing. Biochim Biophys Acta. 1808;2011:236-43.
97. Torres M, Price SL, Fiol-Deroque MA, Marcilla-Etxenike A, Ahyayauch H, Barceló-Coblijn G, et al. Membrane lipid modifications and therapeutic effects mediated by hydroxydocosahexaenoic acid on Alzheimer's disease. Biochim Biophys Acta. 1838;2014:1680-92.
98. Zhang C, Bazan NG. Lipid-mediated cell signaling protects against injury and neurodegeneration. J Nutr. 2010;140:858-63.
99. Hashimoto M, Katakura M, Hossain S, Rahman A, Shimada T, Shido O. Docosahexaenoic acid withstands the Aβ (25-35)-induced neurotoxicity in SH-SY5Y cells. J Nutr Biochem. 2011;22:22-9.
100. Sublimi Saponetti M, Grimaldi M, Scrima M, Albonetti C, Nori SL, Cucolo A. Aggregation of Aβ (25-35) on DOPC and DOPC/DHA bilayers: an atomic force microscopy study. PLoS One. 2014;9:e115780.
101. Calon F, Lim GP, Yang F, Morihara T, Teter B, Ubeda O, et al. Docosahexaenoic acid protects from dendritic pathology in an Alzheimer's disease mouse model. Neuron. 2004;43:633-45.
102. Calon F, Cole G. Neuroprotective action of omega-3 polyunsaturated fatty acids against neurodegenerative diseases: evidence from animal studies. Prostaglandins Leukot Essent Fat Acids. 2007;77:287-93.
103. Lim GP, Calon F, Morihara T, Yang F, Teter B, Ubeda O, et al. A diet enriched with the omega-3 fatty acid docosahexaenoic acid reduces amyloid burden in an aged Alzheimer mouse model. J Neurosci. 2005;25:3032-40.
104. Arsenault D, Julien C, Tremblay C, Calon F. DHA improves cognition and prevents dysfunction of entorhinal cortex neurons in 3xTg-AD mice. PLoS One. 2011;6:e17397.
105. Perez SE, Berg BM, Moore KA, He B, Counts SE, Fritz JJ, et al. DHA diet reduces AD pathology in young APPswe/PS1 delta E9 transgenic mice: possible gender effects. J Neurosci Res. 2010;88:1026-40.
106. Hashimoto M, Tozawa R, Katakura M, Shahdat H, Haque AM, Tanabe Y, et al. Protective effects of prescription n-3 fatty acids against impairment of spatial cognitive learning ability in amyloid β-infused rats. Food Funct. 2011;2:386-94.
107. Green KN, Martinez-Coria H, Khashwji H, Hall EB, Yurko-Mauro KA, Ellis L, et al. Dietary docosahexaenoic acid and docosapentaenoic acid ameliorate amyloid-beta and tau pathology via a mechanism involving presenilin 1 levels. J Neurosci. 2007;27:4385-95.
108. Hooijmans CR, Rutters F, Dederen PJ, Gambarota G, Veltien A, van Groen T, 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;28:16-29.
109. Fiol-deRoque MA, Gutierrez-Lanza R, Terés S, Torres M, Barceló P, Rial RV, et al. Cognitive recovery and restoration of cell proliferation in the dentate gyrus in the 5XFAD transgenic mice model of Alzheimer's disease following 2-hydroxy-DHA treatment. Biogerontology. 2013;14:763-75.
110. Vedin I, Cederholm T, Freund-Levi Y, Basun H, Garlind A, Irving GF, et al. Effects of DHA-rich n-3 fatty acid supplementation on gene expression in blood mononuclear leukocytes: the OmegAD study. PLoS One. 2012;7:e35425.
111. Freund Levi Y, Vedin I, Cederholm T, Basun H, Faxén Irving G, Eriksdotter M, et al. 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. 2014;275:428-36.
112. Cederholm T, Salem Jr N, Palmblad J. ω-3 fatty acids in the prevention of cognitive decline in humans. Adv Nutr. 2013;4:672-6.
113. Quinn JF, Raman R, Thomas RG, Yurko-Mauro K, Nelson EB, Van Dyck C, et al. Docosahexaenoic acid supplementation and cognitive decline in Alzheimer disease: a randomized trial. JAMA. 2010;304:1903-11.
114. Chouinard-Watkins R, Rioux-Perreault C, Fortier M, Tremblay-Mercier J, Zhang Y, et al. Disturbance in uniformly 13C-labelled DHA metabolism in elderly human subjects carrying the apoE ε4 allele. Br J Nutr. 2013;110:1751-9.
115. Vandal M, Alata W, Tremblay C, Rioux-Perreault C, Salem Jr N, Calon F, et al. Reduction in DHA transport to the brain of mice expressing human APOE4 compared to APOE2. J Neurochem. 2014;129:516-26.
116. Conway V, Allard MJ, Minihane AM, Jackson KG, Lovegrove JA, Plourde M. Postprandial enrichment of triacylglycerol-rich lipoproteins with omega-3 fatty acids: lack of an interaction with apolipoprotein E genotype? Lipids Health Dis. 2014;13:148.
117. Dang TM, Conway V, Plourde M. Disrupted fatty acid distribution in HDL and LDL according to apolipoprotein E allele. Nutrition. 2015;31:807-12.
118. Terwel D, Steffensen KR, Verghese PB, Kummer MP, Gustafsson JÅ, Holtzman DM, et al. Critical role of astroglial apolipoprotein E and liver X receptor-α expression for microglial Aβ phagocytosis. J Neurosci. 2011;31:7049-59.
119. Casali BT, Corona AW, Mariani MM, Karlo JC, Ghosal K, Landreth GE. Omega-3 fatty acids augment the actions of nuclear receptor agonists in a mouse model of Alzheimer's disease. J Neurosci. 2015;35:9173-81.
120. Tai LM, Koster KP, Luo J, Lee SH, Wang YT, Collins NC, et al. Amyloid-β pathology and APOE genotype modulate retinoid X receptor agonist activity in vivo. J Biol Chem. 2014;289:30538-55.
121. Conquer JA, Tierney MC, Zecevic J, Bettger WJ, Fisher RH. Fatty acid analysis of blood plasma of patients with Alzheimer's disease, other types of dementia, and cognitive impairment. Lipids. 2000;35:1305-12.
122. Tully AM, Roche HM, Doyle R, Fallon C, Bruce I, Lawlor B, et al. Low serum cholesteryl ester-docosahexaenoic acid levels in Alzheimer's disease: a case-control study. Br J Nutr. 2003;89:483-9.
123. Wang W, Shinto L, Connor WE, Quinn JF. Nutritional biomarkers in Alzheimer's disease: the association between carotenoids, n-3 fatty acids, and dementia severity. J Alzheimers Dis. 2008;13:31-8.
124. Astarita G, Jung KM, Berchtold NC, Nguyen VQ, Gillen DL, Head E, et al. Deficient liver biosynthesis of docosahexaenoic acid correlates with cognitive impairment in Alzheimer's disease. PLoS One. 2010;5:e12538.
125. Plourde M, Fortier M, Vandal M, Tremblay-Mercier J, Freemantle E, Bégin M, et al. Unresolved issues in the link between docosahexaenoic acid and Alzheimer's disease. Prostaglandins Leukot Essent Fatty Acids. 2007;77:301-8.
126. Cole GM, Frautschy SA. Docosahexaenoic acid protects from amyloid and dendritic pathology in an Alzheimer's disease mouse model. Nutr Health. 2006;18:249-59.
127. McGahon BM, Martin DS, Horrobin DF, Lynch MA. Age-related changes in synaptic function: analysis of the effect of dietary supplementation with ω-3 fatty acids. Neuroscience. 1999;94:305-14.
128. Lee LK, Shahar S, Chin AV, Yusoff NA. 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;225:605-12.
129. Fiala M, Halder RC, Sagong B, Ross O, Sayre J, Porter V, et al. ω-3 supplementation increases amyloid-β phagocytosis and resolvin D1 in patients with minor cognitive impairment. FASEB J. 2015;29:2681-9.
130. 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;11:226-35.
131. Jernerén F, Elshorbagy AK, Oulhaj A, Smith SM, Refsum H, Smith AD. Brain atrophy in cognitively impaired elderly: the importance of long-chain ω-3 fatty acids and B vitamin status in a randomized controlled trial. Am J Clin Nutr. 2015;102:215-21.
132. van Neerven S, Kampmann E, Mey J. RAR/RXR and PPAR/RXR signaling in neurological and psychiatric diseases. Prog Neurobiol. 2008;85:433-51.