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


 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 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-β42/40 – Aβ42/40, neurofilament light chain – NfL, progranulin), nutrition (erythrocyte docosahexaenoic acid – DHA, eicosapentaenoic acid – EPA, omega-3 index; plasma homocysteine – Hcy, 25 hydroxyvitamin D), inflammation (plasma tumor necrosis factor receptor – 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, Aβ42/40 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 non-carriers 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.