title: Blood Cell Palmitoleate-Palmitate Ratio Is an Independent Prognostic Factor for Amyotrophic Lateral Sclerosis.
abstract: Growing evidence supports a link between fatty acid metabolism and amyotrophic lateral sclerosis (ALS). Here we determined the fatty acid composition of blood lipids to identify markers of disease progression and survival. We enrolled 117 patients from two clinical centers and 48 of these were age and gender matched with healthy volunteers. We extracted total lipids from serum and blood cells, and separated fatty acid methyl esters by gas chromatography. We measured circulating biochemical parameters indicative of the metabolic status. Association between fatty acid composition and clinical readouts was studied, including ALS functional rating scale-revised (ALSFRS-R), survival, disease duration, site of onset and body mass index. Palmitoleate (16:1) and oleate (18:1) levels, and stearoyl-CoA desaturase indices (16:1/16:0 and 18:1/18:0) significantly increased in blood cells from ALS patients compared to healthy controls. Palmitoleate levels and 16:1/16:0 ratio in blood cells, but not body mass index or leptin concentrations, negatively correlated with ALSFRS-R decline over a six-month period (p<0.05). Multivariate Cox analysis, with age, body mass index, site of onset and ALSFRS-R as covariables, showed that blood cell 16:1/16:0 ratio was an independent prognostic factor for survival (hazard ratio=0.1 per unit of ratio, 95% confidence interval=0.01-0.57, p=0.009). In patients with high 16:1/16:0 ratio, survival at blood collection was extended by 10 months, as compared to patients with low ratio. The 16:1/16:0 index is an easy-to-handle parameter that predicts survival of ALS patients independently of body mass index. It therefore deserves further validation in larger cohorts for being used to assess disease outcome and effects of disease-modifying drugs.
authors.affiliation: INSERM, U1118, Mécanismes Centraux et Périphériques de la Neurodégénerescence, Strasbourg, France; Université de Strasbourg, UMR_S1118, Fédération de Médecine Translationnelle, Strasbourg, France.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Henriques
authors.affiliation: INSERM, Université François-Rabelais, U930, Neurogénétique et Neurométabolomique, Tours, France; CHRU de Tours, Laboratoire de Biochimie et de Biologie Moléculaire, Tours, France.
authors.forename: Hélène
authors.initials: H
authors.lastname: Blasco
authors.affiliation: Hôpitaux Universitaires de Strasbourg, Service de Neurologie, Fédération de Médecine Transrationnelle, Strasbourg, France.
authors.forename: Marie-Céline
authors.initials: MC
authors.lastname: Fleury
authors.affiliation: INSERM, Université François-Rabelais, U930, Neurogénétique et Neurométabolomique, Tours, France; CHRU de Tours, Centre SLA, Tours, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Corcia
authors.affiliation: INSERM, U1118, Mécanismes Centraux et Périphériques de la Neurodégénerescence, Strasbourg, France; Université de Strasbourg, UMR_S1118, Fédération de Médecine Translationnelle, Strasbourg, France; Hôpitaux Universitaires de Strasbourg, Service de Neurologie, Fédération de Médecine Transrationnelle, Strasbourg, France.
authors.forename: Andoni
authors.initials: A
authors.lastname: Echaniz-Laguna
authors.affiliation: INSERM, U1118, Mécanismes Centraux et Périphériques de la Neurodégénerescence, Strasbourg, France; Université de Strasbourg, UMR_S1118, Fédération de Médecine Translationnelle, Strasbourg, France.
authors.forename: Laura
authors.initials: L
authors.lastname: Robelin
authors.affiliation: Hôpitaux Universitaires de Strasbourg, Service de Neurologie, Fédération de Médecine Transrationnelle, Strasbourg, France.
authors.forename: Gabrielle
authors.initials: G
authors.lastname: Rudolf
authors.affiliation: INSERM, U1118, Mécanismes Centraux et Périphériques de la Neurodégénerescence, Strasbourg, France; Université de Strasbourg, UMR_S1118, Fédération de Médecine Translationnelle, Strasbourg, France.
authors.forename: Thiebault
authors.initials: T
authors.lastname: Lequeu
authors.affiliation: Université de Strasbourg, IPHC, Equipe de Chimie Analytique des Molécules BioActives, Illkirch-Graffenstaden, France; CNRS, UMR 7178, Strasbourg, France.
authors.forename: Martine
authors.initials: M
authors.lastname: Bergaentzle
authors.affiliation: INSERM, Université de Strasbourg, UMR_S949, Etablissement Français du Sang - Alsace, Strasbourg, France.
authors.forename: Christian
authors.initials: C
authors.lastname: Gachet
authors.affiliation: Assistance Publique - Hôpitaux de Paris, Hôpital de la Pitié-Salpêtrière, Fédération des Maladies du Système Nerveux, Centre Référent Maladie Rare SLA, Paris, France.
authors.forename: Pierre-François
authors.initials: PF
authors.lastname: Pradat
authors.affiliation: Université de Strasbourg, IPHC, Equipe de Chimie Analytique des Molécules BioActives, Illkirch-Graffenstaden, France; CNRS, UMR 7178, Strasbourg, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Marchioni
authors.affiliation: INSERM, Université François-Rabelais, U930, Neurogénétique et Neurométabolomique, Tours, France; CHRU de Tours, Laboratoire de Biochimie et de Biologie Moléculaire, Tours, France.
authors.forename: Christian R
authors.initials: CR
authors.lastname: Andres
authors.affiliation: Hôpitaux Universitaires de Strasbourg, Service de Neurologie, Fédération de Médecine Transrationnelle, Strasbourg, France.
authors.forename: Christine
authors.initials: C
authors.lastname: Tranchant
authors.affiliation: INSERM, U1118, Mécanismes Centraux et Périphériques de la Neurodégénerescence, Strasbourg, France; Université de Strasbourg, UMR_S1118, Fédération de Médecine Translationnelle, Strasbourg, France.
authors.forename: Jose-Luis
authors.initials: JL
authors.lastname: Gonzalez De Aguilar
authors.affiliation: INSERM, U1118, Mécanismes Centraux et Périphériques de la Neurodégénerescence, Strasbourg, France; Université de Strasbourg, UMR_S1118, Fédération de Médecine Translationnelle, Strasbourg, France.
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Loeffler
mesh_terms: D000328:Adult; D000368:Aged; D000690:Amyotrophic Lateral Sclerosis / Q000097:blood* / Q000401:mortality*; D015992:Body Mass Index; D016022:Case-Control Studies; D018450:Disease Progression; D005229:Fatty Acids, Monounsaturated / Q000097:blood*; D005260:Female; D006801:Humans; D020738:Leptin / Q000097:blood; D008297:Male; D008875:Middle Aged; D019308:Palmitic Acid / Q000097:blood*; D011379:Prognosis; D012720:Severity of Illness Index; D015996:Survival Rate
chemical_list: D005229:Fatty Acids, Monounsaturated; D020738:Leptin; C008757:palmitoleic acid; D019308:Palmitic Acid