Plasma fatty acid lipidomics in amnestic mild cognitive impairment and Alzheimer's disease.

Polyunsaturated fatty acids (PUFA) of the n-3 series have been linked to brain physiology and cognitive decline, but little is known about the other components of the complex fatty acids category. Here, we compared 30 molecular species pertaining to saturated, monounsaturated, polyunsaturated, and trans fatty acids, measured in plasma by gas chromatography, in 14 patients with a diagnosis of amnestic single domain mild cognitive impairment (aMCI), 30 patients with mild Alzheimer's disease (AD), and 30 healthy controls (HC). As no participants showed neuroimaging evidence of cerebrovascular disease, patients could be considered as purely neurodegenerative. We found differences in specific components of almost all fatty acid classes except n-3-polyunsaturated fatty acids. Compared with HC, aMCI and AD patients had higher levels of arachidic (C20:0), erucic (C22:1, n-9), and vaccenic acid (C18:1, n-9) and lower levels of cerotic (C26:0) and linoleic acid (C18:2, n-6). In particular, level of linoleic acid decreased and level of mead acid increased progressively from HC to aMCI to AD patients, and they were also inversely correlated in AD and aMCI patients. In conclusion, we found a previously unrecognized linoleic acid deficiency in the early phase of neurodegeneration that was strongly supported by an increased, compensatory mead acid level. These findings suggest the importance of creating new dietary manipulation strategies to counteract disease progression.

[1]  J. Morris.  The Clinical Dementia Rating (CDR) , 1993, Neurology.

[2]  M. Mega,et al.  The Neuropsychiatric Inventory , 1994, Neurology.

[3]  Zejian Wang,et al.  Neuroprotective effects of arachidonic acid against oxidative stress on rat hippocampal slices. , 2006, Chemico-biological interactions.

[4]  P. Barberger-Gateau,et al.  Fish, docosahexaenoic acid and Alzheimer's disease. , 2009, Progress in lipid research.

[5]  S. Hammarström.  Conversion of 5,8,11-eicosatrienoic acid to leukotrienes C3 and D3. , 1981, The Journal of biological chemistry.

[6]  D. Wilson,et al.  Free fatty acids stimulate the polymerization of tau and amyloid beta peptides. In vitro evidence for a common effector of pathogenesis in Alzheimer's disease. , 1997, The American journal of pathology.

[7]  S. Watkins,et al.  Identification of a Lipokine, a Lipid Hormone Linking Adipose Tissue to Systemic Metabolism , 2008, Cell.

[8]  R. Caterina.  n–3 Fatty Acids in Cardiovascular Disease , 2011 .

[9]  E. Tangalos,et al.  Mild Cognitive Impairment Clinical Characterization and Outcome , 1999 .

[10]  J. Geleijnse,et al.  Effects of n-3 fatty acids on cognitive decline: A randomized, double-blind, placebo-controlled trial in stable myocardial infarction patients , 2011, Alzheimer's & Dementia.

[11]  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.

[12]  N. Salem,et al.  A simplified and efficient method for the analysis of fatty acid methyl esters suitable for large clinical studies Published, JLR Papers in Press, August 1, 2005. DOI 10.1194/jlr.D500022-JLR200 , 2005, Journal of Lipid Research.

[13]  Jean-François Dartigues,et al.  Fish, meat, and risk of dementia: cohort study , 2002, BMJ : British Medical Journal.

[14]  R. Mayeux,et al.  Dietary factors and Alzheimer's disease , 2004, The Lancet Neurology.

[15]  J. Rokach,et al.  Structural Requirements for Activation of the 5-Oxo-6E,8Z, 11Z,14Z-eicosatetraenoic Acid (5-Oxo-ETE) Receptor: Identification of a Mead Acid Metabolite with Potent Agonist Activity , 2008, Journal of Pharmacology and Experimental Therapeutics.

[16]  K. Beyreuther,et al.  Additive effects of fatty acid mixtures on the levels and ratio of amyloid β40/42 peptides differ from the effects of individual fatty acids , 2011, Journal of Neuroscience Research.

[17]  J. Schneider,et al.  Plasma and brain fatty acid profiles in mild cognitive impairment and Alzheimer's disease. , 2012, Journal of Alzheimer's disease : JAD.

[18]  A. Hofman,et al.  Diet and risk of dementia: Does fat matter? , 2002, Neurology.

[19]  M. Boaz,et al.  Association of cholesterol oxidation and abnormalities in fatty acid metabolism in cystic fibrosis. , 2009, The American journal of clinical nutrition.

[20]  D. Bennett,et al.  Consumption of fish and n-3 fatty acids and risk of incident Alzheimer disease. , 2003, Archives of neurology.

[21]  P. Osterrieth.  Le test de copie d'une figure complexe , 1944 .

[22]  H. Iso,et al.  Linoleic Acid, Other Fatty Acids, and the Risk of Stroke , 2002, Stroke.

[23]  Michael Weiner,et al.  Docosahexaenoic acid supplementation and cognitive decline in Alzheimer disease: a randomized trial. , 2010, JAMA.

[24]  D. Bennett,et al.  Dietary fats and the risk of incident Alzheimer disease. , 2003, Archives of neurology.

[25]  E. Schaefer,et al.  Criteria for essential fatty acid deficiency in plasma as assessed by capillary column gas-liquid chromatography. , 1987, Clinical chemistry.

[26]  R S Wilson,et al.  Dietary fat intake and 6-year cognitive change in an older biracial community population , 2004, Neurology.

[27]  M. Morris.  The role of nutrition in Alzheimer’s disease: epidemiological evidence , 2009, European journal of neurology.

[28]  K. Yaffe,et al.  Fish consumption, long-chain omega-3 fatty acids and risk of cognitive decline or Alzheimer disease: a complex association , 2009, Nature Clinical Practice Neurology.

[29]  Olivier Rouaud,et al.  Potential roles of peroxisomes in Alzheimer's disease and in dementia of the Alzheimer's type. , 2012, Journal of Alzheimer's disease : JAD.

[30]  R. W. Evans,et al.  Double bond requirement for the 5-lipoxygenase pathway. , 1985, Prostaglandins.

[31]  M. Folstein,et al.  Clinical diagnosis of Alzheimer's disease , 1984, Neurology.

[32]  C. Caltagirone,et al.  The Mental Deterioration Battery: Normative Data, Diagnostic Reliability and Qualitative Analyses of Cognitive Impairment , 1996 .

[33]  H. Tanila,et al.  Impact of different saturated fatty acid, polyunsaturated fatty acid and cholesterol containing diets on beta-amyloid accumulation in APP/PS1 transgenic mice , 2006, Neurobiology of Disease.

[34]  S. Patil,et al.  Palmitic acid-treated astrocytes induce BACE1 upregulation and accumulation of C-terminal fragment of APP in primary cortical neurons , 2006, Neuroscience Letters.

[35]  T. Montine,et al.  Formation of Highly Reactive A-ring and J-ring Isoprostane-like Compounds (A4/J4-neuroprostanes) in Vivo from Docosahexaenoic Acid* , 2002, The Journal of Biological Chemistry.

[36]  T. Montine,et al.  Formation of Highly Reactive γ-Ketoaldehydes (Neuroketals) as Products of the Neuroprostane Pathway* , 2001, The Journal of Biological Chemistry.

[37]  N. Schupf,et al.  Nutrient intake and plasma β-amyloid , 2012, Neurology.

[38]  J. Lindsay,et al.  Omega-3 fatty acids and risk of dementia: the Canadian Study of Health and Aging. , 2009, The American journal of clinical nutrition.

[39]  Stephen W. Scheff,et al.  Induction of Alzheimer-like β-Amyloid Immunoreactivity in the Brains of Rabbits with Dietary Cholesterol , 1994, Experimental Neurology.

[40]  D. Ma,et al.  Dose‐dependent anticonvulsant effects of linoleic and α‐linolenic polyunsaturated fatty acids on pentylenetetrazol induced seizures in rats , 2009, Epilepsia.

[41]  J. Stroop.  Studies of interference in serial verbal reactions. , 1992 .

[42]  A. Dangour,et al.  Omega 3 fatty acid for the prevention of dementia. , 2006, The Cochrane database of systematic reviews.

[43]  L. Iuliano,et al.  N3 Fatty Acids and Neurodegeneration: Is it Enough to Stop or to Shift? , 2012 .

[44]  G. Lepage,et al.  Direct transesterification of all classes of lipids in a one-step reaction. , 1986, Journal of lipid research.

[45]  A. Folsom,et al.  Plasma n-3 fatty acids and the risk of cognitive decline in older adults: the Atherosclerosis Risk in Communities Study. , 2007, The American journal of clinical nutrition.