Effects of Omega-3 Fatty Acids on Inflammatory Markers in Cerebrospinal Fluid and Plasma in Alzheimer’s Disease: The OmegAD Study

Background: ω-3 fatty acids (ω-3 FAs) found in dietary fish or fish oils are anti-inflammatory agents that may influence Alzheimer’s disease (AD). Objective: To study the effects of dietary ω-3 FA supplementation on inflammatory markers in cerebrospinal fluid (CSF) and plasma from patients with mild to moderate AD. Methods: Thirty-five patients (70.3 ± 8.2 years) were randomized to a daily intake of 2.3 g ω-3 FAs or placebo for 6 months. The inflammatory markers interleukin (IL)-6, tumour necrosis factor-α and soluble interleukin-1 receptor type II (sIL-1RII) were analysed in CSF and plasma at baseline and at 6 months. The AD markers tau-protein, hyperphosphorylated tau-protein and β-amyloid (Aβ1–42) were assessed in CSF. High-sensitivity C-reactive protein was assessed in plasma. A possible relation to the APOE genotype was investigated. Results: There was no significant treatment effect of ω-3 FAs on inflammatory and AD biomarkers in CSF or on inflammatory markers in plasma, nor was there any relation with APOE. A significant correlation was observed at baseline between sIL-1RII and Aβ1–42 levels in CSF. Conclusions: Treatment of AD patients with ω-3 FAs for 6 months did not influence inflammatory or biomarkers in CSF or plasma. The correlation between sIL-1RII and Aβ1–42 may reflect the reciprocal interactions between IL-1 and Aβ peptides.

[1]  K. Blennow,et al.  Increasing CSF phospho-tau levels during cognitive decline and progression to dementia , 2008, Neurobiology of Aging.

[2]  D. Farfara,et al.  Neuroprotective and neurotoxic properties of glial cells in the pathogenesis of Alzheimer's disease , 2008, Journal of cellular and molecular medicine.

[3]  J. Palmblad,et al.  Omega‐3 supplementation in mild to moderate Alzheimer's disease: effects on neuropsychiatric symptoms , 2008, International journal of geriatric psychiatry.

[4]  C. Meinert,et al.  Chronic disease long-term drug prevention trials: Lessons from the Alzheimer’s Disease Anti-inflammatory Prevention Trial (ADAPT) , 2008, Alzheimer's & Dementia.

[5]  L. Horrocks,et al.  Comparison of biochemical effects of statins and fish oil in brain: The battle of the titans , 2007, Brain Research Reviews.

[6]  F. Calderon,et al.  Role of RXR in neurite outgrowth induced by docosahexaenoic acid. , 2007, Prostaglandins, leukotrienes, and essential fatty acids.

[7]  P. Mukherjee,et al.  Docosanoids are multifunctional regulators of neural cell integrity and fate: significance in aging and disease. , 2007, Prostaglandins, leukotrienes, and essential fatty acids.

[8]  R. Tibshirani,et al.  Classification and prediction of clinical Alzheimer's diagnosis based on plasma signaling proteins , 2007, Nature Medicine.

[9]  G. Cole,et al.  Neuroprotective action of omega-3 polyunsaturated fatty acids against neurodegenerative diseases: evidence from animal studies. , 2007, Prostaglandins, leukotrienes, and essential fatty acids.

[10]  S. Volpato,et al.  Plasma cytokines profile in older subjects with late onset Alzheimer's disease or vascular dementia. , 2007, Journal of psychiatric research.

[11]  E. Hjorth,et al.  Inflammation in the nervous system — Physiological and pathophysiological aspects , 2007, Physiology & Behavior.

[12]  B. Winblad,et al.  Studies on brain volume, Alzheimer-related proteins and cytokines in mice with chronic overexpression of IL-1 receptor antagonist , 2007, Journal of cellular and molecular medicine.

[13]  B. de Strooper,et al.  Regulated Intramembrane Proteolysis of the Interleukin-1 Receptor II by α-, β-, and γ-Secretase* , 2007, Journal of Biological Chemistry.

[14]  H. Feldman,et al.  Primary Prevention and Delay of Onset of AD/Dementia , 2007, Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques.

[15]  Noriyuki Matsukawa,et al.  Dietary supplementation of arachidonic and docosahexaenoic acids improves cognitive dysfunction , 2006, Neuroscience Research.

[16]  Lars-Olof Wahlund,et al.  Omega-3 fatty acid treatment in 174 patients with mild to moderate Alzheimer disease: OmegAD study: a randomized double-blind trial. , 2006, Archives of neurology.

[17]  F. Schmitt,et al.  Hippocampal synaptic loss in early Alzheimer's disease and mild cognitive impairment , 2006, Neurobiology of Aging.

[18]  N. Tabet.  Acetylcholinesterase inhibitors for Alzheimer's disease: anti-inflammatories in acetylcholine clothing! , 2006, Age and ageing.

[19]  E. Tobinick,et al.  TNF-alpha modulation for treatment of Alzheimer's disease: a 6-month pilot study. , 2006, MedGenMed : Medscape general medicine.

[20]  R. Mrak,et al.  Potential inflammatory biomarkers in Alzheimer's disease. , 2006, Journal of Alzheimer's disease : JAD.

[21]  W. Mojica,et al.  The Efficacy of Omega–3 Fatty Acids on Cognitive Function in Aging and Dementia: A Systematic Review , 2006, Dementia and Geriatric Cognitive Disorders.

[22]  Fusheng Yang,et al.  Prevention of Alzheimer's disease: Omega-3 fatty acid and phenolic anti-oxidant interventions , 2005, Neurobiology of Aging.

[23]  Charles N Serhan,et al.  A role for docosahexaenoic acid-derived neuroprotectin D1 in neural cell survival and Alzheimer disease. , 2005, The Journal of clinical investigation.

[24]  J. Jia,et al.  Cerebrospinal fluid tau, Aβ1–42 and inflammatory cytokines in patients with Alzheimer's disease and vascular dementia , 2005, Neuroscience Letters.

[25]  M. Schultzberg,et al.  Soluble interleukin-1 receptor type II, IL-18 and caspase-1 in mild cognitive impairment and severe Alzheimer's disease , 2005, Neurochemistry International.

[26]  Farzaneh A. Sorond,et al.  Relation of C-reactive protein to stroke, cognitive disorders, and depression in the general population: systematic review and meta-analysis , 2005, The Lancet Neurology.

[27]  Takashi Morihara,et al.  A Diet Enriched with the Omega-3 Fatty Acid Docosahexaenoic Acid Reduces Amyloid Burden in an Aged Alzheimer Mouse Model , 2005, The Journal of Neuroscience.

[28]  V. Mathura,et al.  Inflammatory cytokine levels correlate with amyloid load in transgenic mouse models of Alzheimer's disease , 2005, Journal of Neuroinflammation.

[29]  D. Gambi,et al.  Acetylcholinesterase inhibitors effects on oncostatin-M, interleukin-1β and interleukin-6 release from lymphocytes of Alzheimer's disease patients , 2005, Experimental Gerontology.

[30]  G. Cole,et al.  NSAID and Antioxidant Prevention of Alzheimer's Disease: Lessons from In Vitro and Animal Models , 2004, Annals of the New York Academy of Sciences.

[31]  A. Hofman,et al.  Inflammatory proteins in plasma and the risk of dementia: the rotterdam study. , 2004, Archives of neurology.

[32]  N. Tabet,et al.  Ibuprofen for Alzheimer's disease. , 2003, The Cochrane database of systematic reviews.

[33]  Simon M Laws,et al.  Expanding the association between the APOE gene and the risk of Alzheimer's disease: possible roles for APOE promoter polymorphisms and alterations in APOE transcription , 2003, Journal of neurochemistry.

[34]  P. Calder.  Dietary modification of inflammation with lipids , 2002, Proceedings of the Nutrition Society.

[35]  M. Tierney,et al.  Fatty acid analysis of blood plasma of patients with alzheimer's disease, other types of dementia, and cognitive impairment , 2000, Lipids.

[36]  K. Blennow,et al.  Quantification of tau phosphorylated at threonine 181 in human cerebrospinal fluid: a sandwich ELISA with a synthetic phosphopeptide for standardization , 2000, Neuroscience Letters.

[37]  J. Venkatraman,et al.  Effects of Dietary ω-3 and ω-6 Lipids and Vitamin E on Serum Cytokines, Lipid Mediators and Anti-DNA Antibodies in a Mouse Model for Rheumatoid Arthritis , 1999 .

[38]  K. Blennow,et al.  Sensitivity, specificity, and stability of CSF-tau in AD in a community-based patient sample. , 1999, Neurology.

[39]  K. Blennow,et al.  Intracerebral Production of Tumor Necrosis Factor-α, a Local Neuroprotective Agent, in Alzheimer Disease and Vascular Dementia , 1999, Journal of Clinical Immunology.

[40]  H. Basun,et al.  Soluble interleukin-1 receptor type II levels are elevated in cerebrospinal fluid in Alzheimer's disease patients , 1999, Brain Research.

[41]  A. Hofman,et al.  Dietary fat intake and the risk of incident dementia in the Rotterdam study , 1997, Annals of neurology.

[42]  K. Blennow,et al.  Tau protein in cerebrospinal fluid: a biochemical marker for axonal degeneration in Alzheimer disease? , 1995, Molecular and chemical neuropathology.

[43]  K. Kristensson,et al.  Fatty acid composition of brain phospholipids in aging and in Alzheimer’s disease , 1991, Lipids.

[44]  D. T. Vernier,et al.  Restriction isotyping of human apolipoprotein E by gene amplification and cleavage with HhaI. , 1990, Journal of lipid research.

[45]  B. Vessby,et al.  Platelet fatty acid composition in relation to fatty acid composition in plasma and to serum lipoprotein lipids in healthy subjects with special reference to the linoleic acid pathway. , 1985, Clinical science.

[46]  M. Åsberg,et al.  A New Depression Scale Designed to be Sensitive to Change , 1979, British Journal of Psychiatry.

[47]  S. Folstein,et al.  "Mini-mental state". A practical method for grading the cognitive state of patients for the clinician. , 1975, Journal of psychiatric research.

[48]  C. Serhan.  Mediator lipidomics. , 2005, Prostaglandins & other lipid mediators.

[49]  J. Venkatraman,et al.  Effects of dietary omega-3 and omega-6 lipids and vitamin E on serum cytokines, lipid mediators and anti-DNA antibodies in a mouse model for rheumatoid arthritis. , 1999, Journal of the American College of Nutrition.

[50]  R. Petersen,et al.  Development of Cognitive Instruments for Use in Clinical Trials of Antidementia Drugs: Additions to the Alzheimer's Disease Assessment Scale That Broaden Its Scope , 1997, Alzheimer disease and associated disorders.

[51]  D. Mostofsky,et al.  Essential fatty acids preparation (SR-3) improves Alzheimer's patients quality of life. , 1996, The International journal of neuroscience.