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
Author:
Giudici Kelly Virecoulon1ORCID, de Souto Barreto Philipe12, Guyonnet Sophie12, Morley John E3, Nguyen Andrew D3ORCID, Aggarwal Geetika3, Parini Angelo4, Li Yan56, Bateman Randall John5, Vellas Bruno12, Vellas Bruno7, Guyonnet Sophie7, Carrié Isabelle7, Brigitte Lauréane7, Faisant Catherine7, Lala Françoise7, Delrieu Julien7, Villars Hélène7, Combrouze Emeline7, Badufle Carole7, Zueras Audrey7, Andrieu Sandrine7, Cantet Christelle7, Morin Christophe7, Abellan Van Kan Gabor7, Dupuy Charlotte7, Rolland Yves7, Caillaud Céline7, Ousset Pierre-Jean7, Bonneville Fabrice7, Cognard Christophe7, Chollet François7, Payoux Pierre7, Voisin Thierry7, Delrieu Julien7, Peiffer Sophie7, Hitzel Anne7, Molinier Laurent7, Derumeaux Hélène7, Costa Nadège7, Perret Bertrand7, Vinel Claire7, Caspar-Bauguil Sylvie7, Olivier-Abbal Pascale7, Andrieu Sandrine7, Cantet Christelle7, Coley Nicola7, Willis Sherry8, Belleville Sylvie9, Gilbert Brigitte9, Fontaine Francine9, Dartigues Jean-François10, Marcet Isabelle10, Delva Fleur10, Foubert Alexandra10, Cerda Sandrine10, Dufouil Carole10, Allard Michèle10, Allard Michèle10, Noëlle-Cuffi Marie11, Costes Corinne11, Rouaud Olivier12, Manckoundia Patrick12, Quipourt Valérie12, Marilier Sophie12, Franon Evelyne12, Ricolfi Frédéric12, Bories Lawrence13, Pader Marie-Laure13, Basset Marie-France13, Lapoujade Bruno13, Faure Valérie13, Li Yung Tong Michael13, Malick-Loiseau Christine13, Cazaban-Campistron Evelyne13, Dubois Dominique13, Desclaux Françoise14, Blatge Colette14, Dantoine Thierry15, Laubarie-Mouret Cécile15, Saulnier Isabelle15, Clément Jean-Pierre15, Picat Marie-Agnès15, Bernard-Bourzeix Laurence15, Willebois Stéphanie15, Désormais Iléana15, Cardinaud Noëlle15, Paule Bonceour Martel Marie15, Monteil Jacques15, Bonnefoy Marc16, Livet Pierre16, Rebaudet Pascale16, Gédéon Claire16, Burdet Catherine16, Terracol Flavien16, Cotton François16, Pesce Alain17, Roth Stéphanie17, Chaillou Sylvie17, Louchart Sandrine17, Sudres Kristel18, Lebrun Nicolas18, Barro-Belaygues Nadège18, Touchon Jacques19, Bennys Karim19, Gabelle Audrey19, Romano Aurélia19, Touati Lynda19, Marelli Cécilia19, Pays Cécile19, Bonafé Alain19, Zanca Michel19, Robert Philippe20, Le Duff Franck20, Gervais Claire20, Gonfrier Sébastien20, Chanalet Stéphane20, Darcourt Jacques20, Gasnier Yannick21, Bordes Serge21, Begorre Danièle21, Carpuat Christian21, Khales Khaled21, Lefebvre Jean-François21, Misbah El Idrissi Samira21, Skolil Pierre21, Salles Jean-Pierre21, Hugon Françoise21, Lehéricy Stéphane22, Chupin Marie22, Mangin Jean-François22, Bouhayia Ali22,
Affiliation:
1. Gerontopole of Toulouse, Institute of Ageing, Toulouse University Hospital (CHU Toulouse) , Toulouse , France 2. CERPOP UMR1295, University of Toulouse III, INSERM, UPS , Toulouse , France 3. Division of Geriatric Medicine, School of Medicine, Saint Louis University , St. Louis, Missouri , USA 4. Institute of Metabolic and Cardiovascular Diseases (I2MC), INSERM UMR 1048, University of Toulouse III Paul Sabatier , Toulouse , France 5. Department of Neurology, Washington University School of Medicine , St. Louis, Missouri , USA 6. Division of Biostatistics, Washington University School of Medicine , St. Louis, Missouri , USA 7. Gerontopole of Toulouse, Toulouse University Hospital (CHU Toulouse) , Toulouse , France 8. University of Seattle, Department of Psychiatry and Behavioral Sciences , Seattle, Washington , United States 9. Université of Montréal, Faculté des arts et des sciences - Département de psychologie , Montréal , Canada 10. Bordeaux University Hospital (CHU Bordeaux), Neurology Department , Bordeaux , France 11. Castres University Hospital (CHU Castres), Neurology Department , Castres , France 12. Dijon Bourgogne University Hospital (CHU Dijon Bourgogne), Dijon , Bourgogne-Franche-Comté , France 13. Foix University Hospital (CHU Foix) , Gerontopole Foix-Ariège , France 14. Lavaur University Hospital (CHU Lavaur) , Pôle Geriatrie, Lavaur , France 15. University Hospital of Limoges (CHU Limoges) , Limoges , France 16. Centre Hospitalier Lyon-Sud , Lyon , France 17. Département des Affaires Sociales et de la Santé, Gouvernement Princier Principalty of Monaco , Monaco 18. Montauban University Hospital (CHU Montauban), Department of Internal Medicine , Montauban , France 19. Montpellier University Hospital (CHU Montpellier), Departement de Neurologie , Montpellier , France 20. University Côte d’Azur , Nice , France 21. Tarbes University Hospital (CHU Tarbes), Pôle Geriatrie , Tarbes , France 22. CATI multicenter neuroimaging platform , Gif-sur-Yvette , France
Abstract
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
Funder
French Ministry of Health University Hospital Center of Toulouse/Gérontopôle, Pierre Fabre Research Institute ExonHit Therapeutics Avid Radiopharmaceuticals University Hospital Center of Toulouse Association Monegasque pour la Recherche sur la maladie d’Alzheimer Unit INSERM-University of Toulouse III National Institute on Aging Saint Louis University Region Occitanie Pyrénées-Méditerranée European Regional Development Fund Alzheimer Prevention in Occitania and Catalonia
Publisher
Oxford University Press (OUP)
Subject
Geriatrics and Gerontology,Aging
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