{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T18:59:29Z","timestamp":1792522769019,"version":"4.5.0"},"reference-count":119,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2025,7,22]],"date-time":"2025-07-22T00:00:00Z","timestamp":1753142400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Universidad Sim\u00f3n Bol\u00edvar"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Alzheimer\u2019s disease (AD) is one of the main causes of dementia, with an exponential increment in its incidence as years go by. However, since pathophysiological mechanisms are complex and multifactorial, therapeutic strategies remain inconclusive and only provide symptomatic relief to patients. In order to solve this problem, new strategies have been investigated over recent years for AD treatment. This field has been reborn due to epidemiological and preclinical findings that demonstrate the fact that omega-3 polyunsaturated fatty acids (\u03c9-3 PUFAs) can be promising therapeutic agents because of their anti-inflammatory, antioxidant, and neurogenic-promoting activities, thus allowing us to classify these molecules as neuroprotectors. Similarly, \u03c9-3 PUFAs perform important actions in the formation of characteristic AD lesions, amyloid-\u03b2 plaques (A\u03b2) and neurofibrillary tangles, reducing the development of these structures. Altogether, the aforementioned actions hinder cognitive decline and possibly reduce AD development. In addition, \u03c9-3 PUFAs modulate the inflammatory response by inhibiting the production of pro-inflammatory molecules and promoting the synthesis of specialised pro-resolving mediators. Consequently, the present review assesses the mechanisms by which \u03c9-3 PUFAs can act as therapeutic molecules and the effectiveness of their use in patients. Clinical evidence so far has shown promising results on \u03c9-3 PUFA effects, both in animal and epidemiological studies, but remains contradictory in clinical trials. More research on these molecules and their neuroprotective effects in AD is needed, as well as the establishment of future guidelines to obtain more reproducible results on this matter.<\/jats:p>","DOI":"10.3390\/molecules30153057","type":"journal-article","created":{"date-parts":[[2025,7,22]],"date-time":"2025-07-22T09:47:06Z","timestamp":1753177626000},"page":"3057","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Neuroprotective Role of Omega-3 Fatty Acids: Fighting Alzheimer\u2019s Disease"],"prefix":"10.3390","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8511-0230","authenticated-orcid":false,"given":"Mervin","family":"Ch\u00e1vez-Castillo","sequence":"first","affiliation":[{"name":"Endocrine and Metabolic Diseases Research Center, School of Medicine, University of Zulia, Maracaibo 4001, Venezuela"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-3959-9820","authenticated-orcid":false,"given":"Mar\u00eda Paula","family":"Gotera","sequence":"additional","affiliation":[{"name":"Endocrine and Metabolic Diseases Research Center, School of Medicine, University of Zulia, Maracaibo 4001, Venezuela"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8030-1780","authenticated-orcid":false,"given":"Pablo","family":"Duran","sequence":"additional","affiliation":[{"name":"Endocrine and Metabolic Diseases Research Center, School of Medicine, University of Zulia, Maracaibo 4001, Venezuela"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda P.","family":"D\u00edaz","sequence":"additional","affiliation":[{"name":"Endocrine and Metabolic Diseases Research Center, School of Medicine, University of Zulia, Maracaibo 4001, Venezuela"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9769-1693","authenticated-orcid":false,"given":"Manuel","family":"Nava","sequence":"additional","affiliation":[{"name":"Endocrine and Metabolic Diseases Research Center, School of Medicine, University of Zulia, Maracaibo 4001, Venezuela"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cl\u00edmaco","family":"Cano","sequence":"additional","affiliation":[{"name":"Endocrine and Metabolic Diseases Research Center, School of Medicine, University of Zulia, Maracaibo 4001, Venezuela"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edgar","family":"D\u00edaz-Camargo","sequence":"additional","affiliation":[{"name":"Facultad de Ciencias Jur\u00eddicas y Sociales, Universidad Sim\u00f3n Bol\u00edvar, C\u00facuta 540006, Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2874-5330","authenticated-orcid":false,"given":"Gabriel","family":"Cano","sequence":"additional","affiliation":[{"name":"Freie Universit\u00e4t Berlin, Institut f\u00fcr Pharmazie, K\u00f6nigin-Luise-Strasse 2-4, 14195 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3692-9917","authenticated-orcid":false,"given":"Raquel","family":"Cano","sequence":"additional","affiliation":[{"name":"Cl\u00ednica General del Norte, Grupo de Estudio e Investigaci\u00f3n en Salud, Barranquilla 080001, Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2169-3208","authenticated-orcid":false,"given":"Diego","family":"Rivera-Porras","sequence":"additional","affiliation":[{"name":"Universidad de la Costa, Departamento de Productividad e Innovaci\u00f3n, Barranquilla 080001, Atl\u00e1ntico, Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1880-8887","authenticated-orcid":false,"given":"Valmore","family":"Berm\u00fadez","sequence":"additional","affiliation":[{"name":"Universidad Sim\u00f3n Bol\u00edvar, Facultad de Ciencias de la Salud, Centro de Investigaciones en Ciencias de la Vida, Barranquilla 080001, Atl\u00e1ntico, Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1016\/j.jtcme.2016.12.003","article-title":"Alzheimer Disease: Clues from traditional and complementary medicine","volume":"7","author":"Cooper","year":"2017","journal-title":"J. Tradit. Complement. Med."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Alzheimer\u2019s Association (2015). 2015 Alzheimer\u2019s disease facts and figures. Alzheimer\u2019s Dement., 11, 332\u2013384.","DOI":"10.1016\/j.jalz.2015.02.003"},{"key":"ref_3","first-page":"105","article-title":"Effectiveness of omega-3 fatty acid supplementation in patients with Alzheimer disease: A systematic review and meta-analysis","volume":"35","year":"2020","journal-title":"Neurologia"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.plipres.2015.12.003","article-title":"The role of omega-3 polyunsaturated fatty acids eicosapentaenoic and docosahexaenoic acids in the treatment of major depression and Alzheimer\u2019s disease: Acting separately or synergistically?","volume":"62","author":"Song","year":"2016","journal-title":"Prog. Lipid Res."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"905","DOI":"10.3945\/an.116.012187","article-title":"Omega-3 polyunsaturated fatty acids and oxylipins in neuroinflammation and management of Alzheimer disease","volume":"7","author":"Devassy","year":"2016","journal-title":"Adv. Nutr."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1186\/s13024-018-0299-8","article-title":"Advances in developing novel therapeutic strategies for Alzheimer\u2019s disease 11 Medical and Health Sciences 1109 Neurosciences","volume":"13","author":"Cao","year":"2018","journal-title":"Mol. Neurodegener."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1007\/s12603-011-0009-5","article-title":"High dietary and plasma levels of the omega-3 fatty acid docosahexaenoic acid are associated with decreased dementia risk: The rancho bernardo study","volume":"15","author":"Lopez","year":"2011","journal-title":"J. Nutr. Health Aging"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Bo, Y., Zhang, X., Wang, Y., You, J., Cui, H., Zhu, Y., Pang, W., Liu, W., Jiang, Y., and Lu, Q. (2017). The n-3 polyunsaturated fatty acids supplementation improved the cognitive function in the Chinese elderly with mild cognitive impairment: A double-blind randomised controlled trial. Nutrients, 9.","DOI":"10.3390\/nu9010054"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1171","DOI":"10.3233\/JAD-170045","article-title":"Mouse Models of Alzheimer\u2019s Disease","volume":"57","author":"Villegas","year":"2017","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Chen, X.Q., and Mobley, W.C. (2019). Alzheimer disease pathogenesis: Insights from molecular and cellular biology studies of oligomeric A\u03b2 and tau species. Front. Neurosci., 13.","DOI":"10.3389\/fnins.2019.00659"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"5541","DOI":"10.2147\/IJN.S200490","article-title":"Alzheimer\u2019s disease: Pathogenesis, diagnostics, and therapeutics","volume":"14","author":"Tiwari","year":"2019","journal-title":"Int. J. Nanomed."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"283","DOI":"10.2174\/1567205014666170417111859","article-title":"Tau in Alzheimer\u2019s Disease: Mechanisms and Therapeutic Strategies","volume":"15","author":"Gao","year":"2018","journal-title":"Curr. Alzheimer Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1515\/bmc-2016-0029","article-title":"Alzheimer\u2019s disease as an inflammatory disease","volume":"8","author":"Perea","year":"2017","journal-title":"Biomol. Concepts"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"508","DOI":"10.2174\/1570159X15666170720095240","article-title":"Microglia and astrocytes in Alzheimer\u2019s disease: Implications for therapy","volume":"16","author":"Fakhoury","year":"2018","journal-title":"Curr. Neuropharmacol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"562","DOI":"10.1111\/jnc.14674","article-title":"Inflammatory mechanisms in neurodegeneration","volume":"149","author":"Nichols","year":"2019","journal-title":"J. Neurochem."},{"key":"ref_16","first-page":"43","article-title":"Alzheimer\u2019s Disease Puzzle: Delving into Pathogenesis Hypotheses","volume":"15","author":"Nasb","year":"2024","journal-title":"Aging Dis."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Ma, Y., Wang, W., Liu, S., Qiao, X., Xing, Y., Zhou, Q., and Zhang, Z. (2023). Epigenetic Regulation of Neuroinflammation in Alzheimer\u2019s Disease. Cells, 13.","DOI":"10.3390\/cells13010079"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1016\/j.neuron.2009.06.026","article-title":"The Role of Apolipoprotein E in Alzheimer\u2019s Disease","volume":"63","author":"Kim","year":"2009","journal-title":"Neuron"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"197","DOI":"10.7150\/thno.79535","article-title":"Role of primary aging hallmarks in Alzheimer\u2019s disease","volume":"13","author":"Zhao","year":"2023","journal-title":"Theranostics"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1016\/j.neurobiolaging.2021.07.014","article-title":"Emerging roles of oxidative stress in brain aging and Alzheimer\u2019s disease","volume":"107","author":"Cotman","year":"2021","journal-title":"Neurobiol. Aging"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Shinohara, M., Sato, N., Shimamura, M., Kurinami, H., Hamasaki, T., Chatterjee, A., Rakugi, H., and Morishita, R. (2014). Possible modification of Alzheimer\u2019s disease by statins in midlife: Interactions with genetic and non-genetic risk factors. Front. Aging Neurosci., 6.","DOI":"10.3389\/fnagi.2014.00071"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Di Liegro, C.M., Schiera, G., Proia, P., and Di Liegro, I. (2019). Physical Activity and Brain Health. Genes, 10.","DOI":"10.3390\/genes10090720"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Vinicius, M., De Mello, C., Vieira, L., Cruz de Souza, L., Gomes, K., and Carvalho, M. (2019). Alzheimer\u2019s disease: Risk factors and potentially protective measures. J. Biomed. Sci., 26.","DOI":"10.1186\/s12929-019-0524-y"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Reemst, K., Broos, J.Y., Abbink, M.R., Cimetti, C., Giera, M., Kooij, G., and Korosi, A. (2022). Early-life stress and dietary fatty acids impact the brain lipid\/oxylipin profile into adulthood, basally and in response to LPS. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.967437"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1186\/s12974-016-0525-7","article-title":"Role of docosahexaenoic acid in the modulation of glial cells in Alzheimer\u2019s disease","volume":"13","year":"2016","journal-title":"J. Neuroinflamm."},{"key":"ref_26","first-page":"467","article-title":"Contribuci\u00f3n de los \u00c1cidos grasos omega-3 para la memoria y la funci\u00f3n cognitiva","volume":"30","author":"Waitzberg","year":"2014","journal-title":"Nutr. Hosp."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1146\/annurev-food-111317-095850","article-title":"Omega-3 Polyunsaturated Fatty Acids and Their Health Benefits","volume":"9","author":"Shahidi","year":"2018","journal-title":"Annu. Rev. Food Sci. Technol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"123","DOI":"10.2174\/1567205012666150921101147","article-title":"Reduction of Oxidative\/Nitrosative Stress in Brain and its Involvement in the Neuroprotective Effect of n-3 PUFA in Alzheimer\u2019s Disease","volume":"13","author":"Serini","year":"2016","journal-title":"Curr. Alzheimer Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1007\/s13668-019-0271-4","article-title":"Diet and Inflammation in Cognitive Ageing and Alzheimer\u2019s Disease","volume":"8","author":"McGrattan","year":"2019","journal-title":"Curr. Nutr. Rep."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2953","DOI":"10.2174\/09298673113209990140","article-title":"n-3 Fatty Acids: Role in Neurogenesis and Neuroplasticity","volume":"20","author":"Crupi","year":"2013","journal-title":"Curr. Med. Chem."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1016\/j.jneuroim.2017.07.005","article-title":"Resolution of inflammation, n \u2212 3 fatty acid supplementation and Alzheimer disease: A narrative review","volume":"310","author":"Fraga","year":"2017","journal-title":"J. Neuroimmunol."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Szczechowiak, K., Diniz, B.S., and Leszek, J. (2019). Diet and Alzheimer\u2019s dementia\u2014Nutritional approach to modulate inflammation. Pharmacol. Biochem. Behav., 184.","DOI":"10.1016\/j.pbb.2019.172743"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1007\/s12975-018-0662-7","article-title":"Post-stroke DHA Treatment Protects Against Acute Ischemic Brain Injury by Skewing Macrophage Polarity Toward the M2 Phenotype","volume":"9","author":"Cai","year":"2018","journal-title":"Transl. Stroke Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"205","DOI":"10.59249\/JNKB9714","article-title":"Natural Bioactive Compounds from Macroalgae and Microalgae for the Treatment of Alzheimer\u2019s Disease: A Review","volume":"97","author":"Lee","year":"2024","journal-title":"Yale J. Biol. Med."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1002\/jnr.22783","article-title":"Docosahexaenoic acid modulates inflammatory and antineurogenic functions of activated microglial cells","volume":"90","author":"Mancini","year":"2012","journal-title":"J. Neurosci. Res."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Lee, J.K., and Kim, N.J. (2017). Recent advances in the inhibition of p38 MAPK as a potential strategy for the treatment of Alzheimer\u2019s disease. Molecules, 22.","DOI":"10.3390\/molecules22081287"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1105","DOI":"10.1042\/BST20160474","article-title":"Omega-3 fatty acids and inflammatory processes: From molecules to man","volume":"45","author":"Calder","year":"2017","journal-title":"Biochem. Soc. Trans."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Li, C., Wu, X., Liu, S., Shen, D., Zhu, J., and Liu, K. (2020). Role of Resolvins in the Inflammatory Resolution of Neurological Diseases. Front. Pharmacol., 11.","DOI":"10.3389\/fphar.2020.00612"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1016\/j.bbi.2018.02.015","article-title":"Chemerin suppresses neuroinflammation and improves neurological recovery via CaMKK2\/AMPK\/Nrf2 pathway after germinal matrix hemorrhage in neonatal rats","volume":"70","author":"Zhang","year":"2018","journal-title":"Brain Behav. Immun."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.cmet.2013.10.006","article-title":"Resolvins, specialised proresolving lipid mediators, and their potential roles in metabolic diseases","volume":"19","author":"Spite","year":"2014","journal-title":"Cell Metab."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1016\/j.plefa.2010.02.003","article-title":"Resolvins and protectins: Natural pharmacophores for resolution biology","volume":"82","author":"Levy","year":"2010","journal-title":"Prostaglandins Leukot. Essent. Fat. Acids"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.mam.2018.09.003","article-title":"Docosanoids and elovanoids from omega-3 fatty acids are pro-homeostatic modulators of inflammatory responses, cell damage and neuroprotection","volume":"64","author":"Bazan","year":"2018","journal-title":"Mol. Asp. Med."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"2733","DOI":"10.1007\/s12035-015-9544-0","article-title":"Pro-Resolving Lipid Mediators Improve Neuronal Survival and Increase A\u03b242 Phagocytosis","volume":"53","author":"Zhu","year":"2016","journal-title":"Mol. Neurobiol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"697","DOI":"10.3233\/JAD-130131","article-title":"Omega-3 fatty acids enhance phagocytosis of alzheimer\u2019s disease-related amyloid-\u03b242 by human microglia and decrease inflammatory markers","volume":"35","author":"Hjorth","year":"2013","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"4853","DOI":"10.1021\/acs.jafc.8b00836","article-title":"Neuroprotective Effect of Alpha-Linolenic Acid against A\u03b2-Mediated Inflammatory Responses in C6 Glial Cell","volume":"66","author":"Lee","year":"2018","journal-title":"J. Agric. Food Chem."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"759","DOI":"10.1016\/j.bcp.2013.07.002","article-title":"Resolvin D1-mediated NOX2 inactivation rescues macrophages undertaking efferocytosis from oxidative stress-induced apoptosis","volume":"86","author":"Lee","year":"2013","journal-title":"Biochem. Pharmacol."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Suzumura, A., Terao, R., and Kaneko, H. (2020). Protective effects and molecular signaling of n-3 fatty acids on oxidative stress and inflammation in retinal diseases. Antioxidants, 9.","DOI":"10.3390\/antiox9100920"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"9634803","DOI":"10.1155\/2017\/9634803","article-title":"Maresin 1 Ameliorates Lung Ischemia\/Reperfusion Injury by Suppressing Oxidative Stress via Activation of the Nrf-2-Mediated HO-1 Signaling Pathway","volume":"2017","author":"Sun","year":"2017","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/j.pneurobio.2018.04.001","article-title":"Regulation and function of neurogenesis in the adult mammalian hypothalamus","volume":"170","author":"Yoo","year":"2018","journal-title":"Prog. Neurobiol."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Dyall, S.C. (2015). Long-chain omega-3 fatty acids and the brain: A review of the independent and shared effects of EPA, DPA and DHA. Front. Aging Neurosci., 7.","DOI":"10.3389\/fnagi.2015.00052"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"804","DOI":"10.3945\/an.117.016261","article-title":"Nutritional factors affecting adult neurogenesis and cognitive function","volume":"8","author":"Poulose","year":"2017","journal-title":"Adv. Nutr."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/j.brainres.2007.08.089","article-title":"Oral supplementation with docosahexaenoic acid and uridine-5\u2032-monophosphate increases dendritic spine density in adult gerbil hippocampus","volume":"1182","author":"Sakamoto","year":"2007","journal-title":"Brain Res."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"510","DOI":"10.1111\/j.1471-4159.2009.06335.x","article-title":"Docosahexaenoic acid promotes hippocampal neuronal development and synaptic function","volume":"111","author":"Cao","year":"2009","journal-title":"J. Neurochem."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"D\u00edaz, M., Mesa-Herrera, F., and Mar\u00edn, R. (2021). Dha and its elaborated modulation of antioxidant defenses of the brain: Implications in aging and ad neurodegeneration. Antioxidants, 10.","DOI":"10.3390\/antiox10060907"},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Eto, M., Hashimoto, T., Shimizu, T., and Iwatsubo, T. (2019). Characterization of the unique in Vitro effects of unsaturated fatty acids on the formation of amyloid \u03b2 fibrils. PLoS ONE, 14.","DOI":"10.1371\/journal.pone.0219465"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"534","DOI":"10.1139\/bcb-2015-0149","article-title":"Eicosapentaenoic acid and docosahexaenoic acid increase the degradation of amyloid-\u03b2 by affecting insulin-degrading enzyme","volume":"94","author":"Grimm","year":"2016","journal-title":"Biochem. Cell Biol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"552","DOI":"10.1016\/j.nbd.2015.09.002","article-title":"Dietary DHA supplementation in an APP\/PS1 transgenic rat model of AD reduces behavioral and A\u03b2 pathology and modulates A\u03b2 oligomerisation","volume":"82","author":"Teng","year":"2015","journal-title":"Neurobiol. Dis."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"115102","DOI":"10.1063\/1.5012032","article-title":"Mechanism by which DHA inhibits the aggregation of KLVFFA peptides: A molecular dynamics study","volume":"148","author":"Zhou","year":"2018","journal-title":"J. Chem. Phys."},{"key":"ref_59","first-page":"289","article-title":"Effects of docosahexaenoic acid on in vitro amyloid beta peptide 25\u201335 fibrillation","volume":"1791","author":"Hashimoto","year":"2009","journal-title":"Biochim. Biophys. Acta (BBA)\u2014Mol. Cell Biol. Lipids"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1080\/07388551.2016.1207153","article-title":"Docosahexaenoic acid: One molecule diverse functions","volume":"37","author":"Hashimoto","year":"2017","journal-title":"Crit. Rev. Biotechnol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"14299","DOI":"10.1523\/JNEUROSCI.3593-07.2007","article-title":"Omega-3 fatty acid docosahexaenoic acid increases SorLA\/LR11, a sorting protein with reduced expression in sporadic Alzheimer\u2019s disease (AD): Relevance to AD prevention","volume":"27","author":"Ma","year":"2007","journal-title":"J. Neurosci."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1580","DOI":"10.1073\/pnas.0337683100","article-title":"Short-term administration of omega 3 fatty acids from fish oil results in increased transthyretin transcription in old rat hippocampus","volume":"100","author":"Kitajka","year":"2003","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"4385","DOI":"10.1523\/JNEUROSCI.0055-07.2007","article-title":"Dietary docosahexaenoic acid and docosapentaenoic acid ameliorate amyloid-\u03b2 and tau pathology via a mechanism involving presenilin 1 levels","volume":"27","author":"Green","year":"2007","journal-title":"J. Neurosci."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"14028","DOI":"10.1074\/jbc.M110.182329","article-title":"Docosahexaenoic acid reduces amyloid \u03b2 production via multiple pleiotropic mechanisms","volume":"286","author":"Grimm","year":"2011","journal-title":"J. Biol. Chem."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1039\/C7FO01342F","article-title":"Comparative study of the effects of phosphatidylcholine rich in DHA and EPA on Alzheimer\u2019s disease and the possible mechanisms in CHO-APP\/PS1 cells and SAMP8 mice","volume":"9","author":"Che","year":"2018","journal-title":"Food Funct."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1073\/pnas.0503839103","article-title":"Nonsteroidal anti-inflammatory drugs repress \u03b2-secretase gene promoter activity by the activation of PPAR\u03b3","volume":"103","author":"Sastre","year":"2006","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"9796","DOI":"10.1523\/JNEUROSCI.23-30-09796.2003","article-title":"Nonsteroidal Anti-Inflammatory Drugs and Peroxisome Proliferator-Activated Receptor-\u03b3 Agonists Modulate Immunostimulated Processing of Amyloid Precursor Protein through Regulation of \u03b2-Secretase","volume":"23","author":"Sastre","year":"2003","journal-title":"J. Neurosci."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1051\/rnd:2005046","article-title":"Docosahexaenoic acid affects cell signaling by altering lipid rafts","volume":"45","author":"Stillwell","year":"2005","journal-title":"Reprod. Nutr. Dev."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1680","DOI":"10.1016\/j.bbamem.2013.12.016","article-title":"Membrane lipid modifications and therapeutic effects mediated by hydroxydocosahexaenoic acid on Alzheimer\u2019s disease","volume":"1838","author":"Torres","year":"2014","journal-title":"Biochim. Biophys. Acta (BBA)\u2014Biomembr."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"777","DOI":"10.1038\/ncomms1781","article-title":"Soluble amyloid precursor protein-\u03b1 modulates \u03b2-secretase activity and amyloid-\u03b2 2 generation","volume":"3","author":"Obregon","year":"2012","journal-title":"Nat. Commun."},{"key":"ref_71","first-page":"274128","article-title":"Amyloid-beta peptide, oxidative stress and inflammation in Alzheimer\u2019s disease: Potential neuroprotective effects of omega-3 polyunsaturated fatty acids","volume":"2010","author":"Dyall","year":"2010","journal-title":"Int. J. Alzheimer\u2019s Dis."},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Zhao, Y., Calon, F., Julien, C., Winkler, J.W., Petasis, N.A., Lukiw, W.J., and Bazan, N.G. (2011). Docosahexaenoic acid-derived neuroprotectin D1 induces neuronal survival via secretase- and PPAR\u03b3-mediated mechanisms in Alzheimer\u2019s disease models. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0015816"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1146\/annurev.nutr.012809.104635","article-title":"Docosahexaenoic acid signalolipidomics in nutrition: Significance in aging, neuroinflammation, macular degeneration, Alzheimer\u2019s, and other neurodegenerative diseases","volume":"31","author":"Bazan","year":"2011","journal-title":"Annu. Rev. Nutr."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1007\/s12035-011-8174-4","article-title":"Neuroprotectin D1 induces neuronal survival and downregulation of amyloidogenic processing in Alzheimer\u2019s disease cellular models","volume":"43","author":"Stark","year":"2011","journal-title":"Mol. Neurobiol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"2774","DOI":"10.1172\/JCI25420","article-title":"A role for docosahexaenoic acid-derived neuroprotectin D1 in neural cell survival and Alzheimer disease","volume":"115","author":"Lukiw","year":"2005","journal-title":"J. Clin. Investig."},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Yin, P., Wang, X., Wang, S., Wei, Y., Feng, J., and Zhu, M. (2019). Maresin 1 Improves Cognitive Decline and Ameliorates Inflammation in a Mouse Model of Alzheimer\u2019s Disease. Front. Cell. Neurosci., 13.","DOI":"10.3389\/fncel.2019.00466"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"392","DOI":"10.1007\/s12035-010-8137-1","article-title":"Why pleiotropic interventions are needed for alzheimer\u2019s disease","volume":"41","author":"Frautschy","year":"2010","journal-title":"Mol. Neurobiol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"2653","DOI":"10.2741\/3878","article-title":"Omega-3 polyunsaturated fatty acids in the brain: Metabolism and neuroprotection","volume":"16","author":"Zhang","year":"2011","journal-title":"Front. Biosci."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"9078","DOI":"10.1523\/JNEUROSCI.1071-09.2009","article-title":"\u03b2-Amyloid oligomers induce phosphorylation of tau and inactivation of insulin receptor substrate via c-Jun N-terminal kinase signaling: Suppression by omega-3 fatty acids and curcumin","volume":"29","author":"Ma","year":"2009","journal-title":"J. Neurosci."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"1618","DOI":"10.1007\/s12035-018-1185-7","article-title":"DHA Selectively Protects SAMP-8-Associated Cognitive Deficits Through Inhibition of JNK","volume":"56","author":"Vela","year":"2019","journal-title":"Mol. Neurobiol."},{"key":"ref_81","doi-asserted-by":"crossref","unstructured":"Toral-Rios, D., Pichardo-Rojas, P.S., Alonso-Vanegas, M., and Campos-Pe\u00f1a, V. (2020). GSK3\u03b2 and Tau Protein in Alzheimer\u2019s Disease and Epilepsy. Front. Cell. Neurosci., 14.","DOI":"10.3389\/fncel.2020.00019"},{"key":"ref_82","first-page":"422","article-title":"Preparation of 99mTc-EDTA-MN and its bioimaging in mouse","volume":"18","author":"Qi","year":"2015","journal-title":"Chin. J. Lung Cancer"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1016\/j.nrl.2014.02.003","article-title":"Treatment of Alzheimer disease using combination therapy with plasma exchange and haemapheresis with albumin and intravenous immunoglobulin: Rationale and treatment approach of the AMBAR (Alzheimer Management By Albumin Replacement) study","volume":"31","author":"Boada","year":"2016","journal-title":"Neurolog\u00eda"},{"key":"ref_84","doi-asserted-by":"crossref","unstructured":"Panza, F., Solfrizzi, V., Seripa, D., Imbimbo, B.P., Lozupone, M., Santamato, A., Zecca, C., Barulli, M.R., Bellomo, A., and Pilotto, A. (2016). Tau-Centric Targets and Drugs in Clinical Development for the Treatment of Alzheimer\u2019s Disease. BioMed Res. Int., 2016.","DOI":"10.1155\/2016\/3245935"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1016\/j.nurt.2008.05.008","article-title":"5-HT6 Receptor Antagonists as Novel Cognitive Enhancing Agents for Alzheimer\u2019s Disease","volume":"5","author":"Upton","year":"2008","journal-title":"Neurotherapeutics"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1186\/s13195-023-01169-x","article-title":"Masitinib for mild-to-moderate Alzheimer\u2019s disease: Results from a randomised, placebo-controlled, phase 3, clinical trial","volume":"15","author":"Dubois","year":"2023","journal-title":"Alzheimer\u2019s Res. Ther."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"100257","DOI":"10.1016\/j.metop.2023.100257","article-title":"Prevention of Alzheimer\u2019s disease through diet: An exploratory review","volume":"20","author":"Bhuiyan","year":"2023","journal-title":"Metab. Open"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"a1344","DOI":"10.1136\/bmj.a1344","article-title":"Adherence to Mediterranean diet and health status: Meta-analysis","volume":"337","author":"Sofi","year":"2008","journal-title":"BMJ"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"161","DOI":"10.3109\/00207454.2016.1155572","article-title":"Alzheimer\u2019s disease and diet: A systematic review","volume":"127","author":"Yusufov","year":"2017","journal-title":"Int. J. Neurosci."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1007\/s13668-013-0070-2","article-title":"DASH and Mediterranean-Type Dietary Patterns to Maintain Cognitive Health","volume":"3","author":"Tangney","year":"2014","journal-title":"Curr. Nutr. Rep."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"154","DOI":"10.3945\/an.114.007617","article-title":"Dietary patterns, cognitive decline, and dementia: A systematic review","volume":"6","author":"Berendsen","year":"2015","journal-title":"Adv. Nutr."},{"key":"ref_92","doi-asserted-by":"crossref","unstructured":"Passeri, E., Elkhoury, K., Morsink, M., Broersen, K., Linder, M., Tamayol, A., Malaplate, C., Yen, F.T., and Arab-Tehrany, E. (2022). Alzheimer\u2019s Disease: Treatment Strategies and Their Limitations. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms232213954"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1007\/s12031-021-01922-7","article-title":"Emerging Novel Approaches for the Enhanced Delivery of Natural Products for the Management of Neurodegenerative Diseases","volume":"72","author":"Bandiwadekar","year":"2022","journal-title":"J. Mol. Neurosci."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/j.archger.2015.12.003","article-title":"Diet, lifestyle and cognitive function in old Chinese adults","volume":"63","author":"Dong","year":"2016","journal-title":"Arch. Gerontol. Geriatr."},{"key":"ref_95","doi-asserted-by":"crossref","unstructured":"Suh, S.W., Lim, E., Burm, S.Y., Lee, H., Bae, J.B., Han, J.W., and Kim, K.W. (2024). The influence of n-3 polyunsaturated fatty acids on cognitive function in individuals without dementia: A systematic review and dose\u2013response meta-analysis. BMC Med., 22.","DOI":"10.1186\/s12916-024-03296-0"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1016\/j.jalz.2016.06.2359","article-title":"Mediterranean diet, micronutrients and macronutrients, and MRI measures of cortical thickness","volume":"13","author":"Staubo","year":"2017","journal-title":"Alzheimer\u2019s Dement."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"1545","DOI":"10.1001\/archneur.63.11.1545","article-title":"Plasma phosphatidylcholine docosahexaenoic acid content and risk of dementia and alzheimer disease: The framingham heart study","volume":"63","author":"Schaefer","year":"2006","journal-title":"Arch. Neurol."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"1103","DOI":"10.1093\/ajcn\/85.4.1103","article-title":"Plasma n-3 fatty acids and the risk of cognitive decline in older adults: The atherosclerosis risk in communities study","volume":"85","author":"Beydoun","year":"2007","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"3624","DOI":"10.3390\/nu6093624","article-title":"Fatty acid status and its relationship to cognitive decline and homocysteine levels in the elderly","volume":"6","author":"Baierle","year":"2014","journal-title":"Nutrients"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"e004850","DOI":"10.1136\/bmjopen-2014-004850","article-title":"Nutrient intake and brain biomarkers of Alzheimer\u2019s disease in at-risk cognitively normal individuals: A cross-sectional neuroimaging pilot study","volume":"4","author":"Mosconi","year":"2014","journal-title":"BMJ Open"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"1208","DOI":"10.1001\/jamaneurol.2016.1924","article-title":"Association of serum docosahexaenoic acid with cerebral amyloidosis","volume":"73","author":"Yassine","year":"2016","journal-title":"JAMA Neurol."},{"key":"ref_102","doi-asserted-by":"crossref","unstructured":"Loong, S., Barnes, S., Gatto, N.M., Chowdhury, S., and Lee, G.J. (2023). Omega-3 Fatty Acids, Cognition, and Brain Volume in Older Adults. Brain Sci., 13.","DOI":"10.3390\/brainsci13091278"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"1096","DOI":"10.1016\/j.ajcnut.2023.04.001","article-title":"The Relationship of Omega-3 Fatty Acids with Dementia and Cognitive Decline: Evidence from Prospective Cohort Studies of Supplementation, Dietary Intake, and Blood Markers","volume":"117","author":"Wei","year":"2023","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_104","doi-asserted-by":"crossref","unstructured":"Sala-Vila, A., Tintle, N., Westra, J., and Harris, W.S. (2023). Plasma Omega-3 Fatty Acids and Risk for Incident Dementia in the UK Biobank Study: A Closer Look. Nutrients, 15.","DOI":"10.3390\/nu15234896"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"1763","DOI":"10.1007\/s00394-019-02126-x","article-title":"Polyunsaturated fatty acids and risk of Alzheimer\u2019s disease: A Mendelian randomization study","volume":"59","author":"Tomata","year":"2020","journal-title":"Eur. J. Nutr."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1016\/S1474-4422(17)30040-6","article-title":"Effect of long-term omega 3 polyunsaturated fatty acid supplementation with or without multi-domain intervention on cognitive function in elderly adults with memory complaints (MAPT): A randomised, placebo-controlled trial","volume":"16","author":"Andrieu","year":"2017","journal-title":"Lancet Neurol."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"71","DOI":"10.3233\/JAD-180209","article-title":"Effects of a 3-Year Multi-Domain Intervention with or without Omega-3 Supplementation on Cognitive Functions in Older Subjects with Increased CAIDE Dementia Scores","volume":"64","author":"Chhetri","year":"2018","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"988","DOI":"10.1007\/s12603-017-0957-5","article-title":"Cognitive changes with omega-3 polyunsaturated fatty acids in non-demented older adults with low omega-3 index","volume":"21","author":"Hooper","year":"2017","journal-title":"J. Nutr. Health Aging"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1111\/ggi.12691","article-title":"Beneficial effects of dietary docosahexaenoic acid intervention on cognitive function and mental health of the oldest elderly in Japanese care facilities and nursing homes","volume":"17","author":"Hashimoto","year":"2017","journal-title":"Geriatr. Gerontol. Int."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"548","DOI":"10.1038\/s41430-019-0544-4","article-title":"Effect of n-3 long-chain polyunsaturated fatty acids on mild cognitive impairment: A meta-analysis of randomized clinical trials","volume":"74","author":"Zhang","year":"2020","journal-title":"Eur. J. Clin. Nutr."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"330","DOI":"10.3945\/ajcn.115.124081","article-title":"Intakes of fish and polyunsaturated fatty acids and mild-to-severe cognitive impairment risks: A dose-response meta-analysis of 21 cohort studies","volume":"103","author":"Zhang","year":"2016","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"111355","DOI":"10.1016\/j.nut.2021.111355","article-title":"Dietary fatty acids and risk for Alzheimer\u2019s disease, dementia, and mild cognitive impairment: A prospective cohort meta-analysis","volume":"90","author":"Zhu","year":"2021","journal-title":"Nutrition"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.neubiorev.2014.11.008","article-title":"Omega-3 fatty acids intake and risks of dementia and Alzheimer\u2019s disease: A meta-analysis","volume":"48","author":"Wu","year":"2015","journal-title":"Neurosci. Biobehav. Rev."},{"key":"ref_114","first-page":"CD009002","article-title":"Omega 3 fatty acids for the treatment of dementia","volume":"2016","author":"Burckhardt","year":"2016","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1002\/npr2.12455","article-title":"The effects of omega-3, DHA, EPA, Souvenaid\u00ae in Alzheimer\u2019s disease: A systematic review and meta-analysis","volume":"44","author":"Srinivas","year":"2024","journal-title":"Neuropsychopharmacol. Rep."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"e2426872","DOI":"10.1001\/jamanetworkopen.2024.26872","article-title":"\u03c9-3 PUFA for Secondary Prevention of White Matter Lesions and Neuronal Integrity Breakdown in Older Adults: A Randomised Clinical Trial","volume":"7","author":"Shinto","year":"2024","journal-title":"JAMA Netw. 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Health Aging"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"e027167","DOI":"10.1136\/bmjopen-2018-027167","article-title":"Associations and effects of omega-3 polyunsaturated fatty acids on cognitive function and mood in healthy adults: A protocol for a systematic review of observational and interventional studies","volume":"9","author":"Carney","year":"2019","journal-title":"BMJ Open"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"e00570","DOI":"10.1016\/j.neurot.2025.e00570","article-title":"Maximizing the benefit and managing the risk of anti-amyloid monoclonal antibody therapy for Alzheimer\u2019s disease: Strategies and research directions","volume":"22","author":"Cummings","year":"2025","journal-title":"Neurotherapeutics"}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/30\/15\/3057\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:13:43Z","timestamp":1760033623000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/30\/15\/3057"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,22]]},"references-count":119,"journal-issue":{"issue":"15","published-online":{"date-parts":[[2025,8]]}},"alternative-id":["molecules30153057"],"URL":"https:\/\/doi.org\/10.3390\/molecules30153057","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7,22]]}}}