TNFR-1 and GDF-15 Are Associated With Plasma Neurofilament Light Chain and Progranulin Among Community-Dwelling Older Adults: A Secondary Analysis of the MAPT Study
Kelly Virecoulon Giudici, Philipe de Souto Barreto, Sophie Guyonnet, John E. Morley, Andrew D. Nguyen, Geetika Aggarwal, Angelo Parini, Yan Li, Randall J. Bateman, Bruno Vellas, MAPT/DSA Group, Bruno Vellas, Sophie Guyonnet, Isabelle Carrié, Lauréane Brigitte, Catherine Faisant, Françoise Lala, Julien Delrieu, Hélène Villars, Emeline Combrouze, Carole Badufle, Audrey Zueras, Sandrine Andrieu, Christelle Cantet, Christophe Morin, Gabor Abellán van Kan, Charlotte Dupuy, Yves Rolland, Céline Caillaud, Pierre‐Jean Ousset, Fabrice Bonneville, Christophe Cognard, François Chollet, Pierre Payoux, Thierry Voisin, Julien Delrieu, Sophie Peiffer, Anne Hitzel, Laurent Molinier, Hélène Derumeaux, Nadège Costa, Bertrand Perret, Claire Vinel, Sylvie Caspar‐Bauguil, Pascale Olivier, Sandrine Andrieu, Christelle Cantet, Nicola Coley, Sherry L. Willis, Sylvie Belleville, Brigitte Gilbert, Francine Fontaine, Jean‐François Dartigues, Isabelle Marcet, Fleur Delva, Alexandra Foubert, Sandrine Cerda, Carole Dufouil, Michèle Allard, Michèle Allard, Marie Noëlle-Cuffi, Corinne Costes, Olivier Rouaud, Patrick Manckoundia, Valérie Quipourt, Sophie Marilier, Evelyne Franon, F. Ricolfi, Lawrence Bories, Marie-Laure Pader, Marie-France Basset, Bruno Lapoujade, Valérie Faure, Michael Li Yung Tong, Christine Malick-Loiseau, Evelyne Cazaban-Campistron, Dominique Dubois, Françoise Desclaux, Colette Blatge, Thierry Dantoine, Cécile Laubarie-Mouret, Isabelle Saulnier, Jean‐Pierre Clément, Marie-Agnès Picat, Laurence Bernard‐Bourzeix, Stéphanie Willebois, Ileana Désormais, Noëlle Cardinaud, Marie Martel, Jacques Monteil, Marc Bonnefoy, Pierre Livet, Pascale Rebaudet, Claire Gédéon, Catherine Burdet, Flavien Terracol, François Cotton, Alain Pesce, Stéphanie Roth, Sylvie Chaillou
Abstract
There is growing evidence that cognitive decline can be affected by both nutritional aspects and inflammation. Plasma neurodegenerative biomarkers stand out as minimally invasive useful measures to monitor the potential risk of cognitive decline. This study aimed to investigate the associations between biomarkers of neurodegeneration, nutrition, and inflammation among community-dwelling older adults, and to verify if associations differed according to apolipoprotein E (APOE) ε4 status. This cross-sectional analysis included 475 participants ≥70 years old from the Multidomain Alzheimer Preventive Trial (MAPT), mean age 76.8 years (SD = 4.5), 59.4% women. Biomarkers of neurodegeneration (plasma amyloid-β 42/40-Aβ 42/40, neurofilament light chain-NfL, progranulin), nutrition (erythrocyte docosahexaenoic acid, eicosapentaenoic acid, omega-3 index; plasma homocysteine-Hcy, 25 hydroxyvitamin D), inflammation (plasma tumor necrosis factor receptor 1-TNFR-1, monocyte chemoattractant protein 1-MCP-1, interleukin 6-IL-6), and cellular stress (plasma growth differentiation factor 15-GDF-15) were assessed. Linear regression analyses were performed to investigate the associations between nutritional and inflammatory biomarkers (independent variables) and neurodegenerative biomarkers (dependent variables), with adjustments for age, sex, education, body mass index, physical activity, allocation to MAPT groups, and APOE ε4 status. After adjusting for confounders, Aβ 42/40 was not associated with nutritional or inflammatory markers. NfL was positively associated with GDF-15, TNFR-1, IL-6, and Hcy. Progranulin was positively associated with GDF-15, TNFR-1, and MCP-1. Analyses restricted to APOE ε4 carriers (n = 116; 26.9%) or noncarriers were mostly similar. Our cross-sectional study with community-dwelling older adults corroborates previous evidence that inflammatory pathways are associated to plasma markers of neurodegeneration. Clinical Trials Registration Number: NCT00672685.