Autor segons l'article: Gutierrez-Tordera, L; Panisello, L; García-Gonzalez, P; Ruiz, A; Cantero, JL; Rojas-Criollo, M; Mursil, M; Atienza, M; Novau-Ferré, N; Mateu-Fabregat, J; Mostafa, H; Puig, D; Folch, J; Rashwan, H; Marquié, M; Boada, M; Papandreou, C; Bulló, M
Departament: Bioquímica i Biotecnologia
Autor/s de la URV: Abdellatif Fatahallah Ibrahim Mahmoud, Hatem / Bulló Bonet, Mònica / Folch Lopez, Jaume / GUTIERREZ TORDERA, LAIA / Mateu Fabregat, Javier / MURSIL, MUHAMMAD / Novau Ferré, Nil / Panisello Melo, Laura / Puig Valls, Domènec Savi / Rojas Criollo, Melina Isabella
Paraules clau: Biomarkers; Blood; Dementia; Good health and well-being; Metabolomic; Metabolomics; Mild cognitive impairment; Predic; Sensitivity
Resum: Background Substantial evidence supports the relationship between peripheral insulin resistance (IR) and the development of Alzheimer's disease (AD)-dementia. However, the mechanisms explaining these associations are only partly understood. We aimed to identify a metabolic signature of IR associated with the progression from mild cognitive impairment (MCI) to AD-dementia. Methods This is a case-control study on 400 MCI subjects, free of type 2 diabetes, within the ACE cohort, including individuals ATN + and ATN-. After a median of 2.1 years of follow-up, 142 subjects converted to AD-dementia. IR was assessed using the homeostasis model assessment for insulin resistance (HOMA-IR). A targeted multiplatform approach profiled over 600 plasma metabolites. Elastic net penalized linear regression with 10-fold cross-validation was employed to select those metabolites associated with HOMA-IR. The prediction ability of the signature was assessed using support vector machine and performance metrics. The metabolic signature was associated with AD-dementia risk using a multivariable Cox regression model. Using counterfactual-based mediation analysis, we investigated the mediation role of the metabolic signature between HOMA-IR and AD-dementia. The metabolic pathways in which the metabolites were involved were identified using MetaboAnalyst. Results The metabolic signature comprised 18 metabolites correlated with HOMA-IR. After adjustments by confounders, the signature was associated with increased AD-dementia risk (HR = 1.234; 95% CI = 1.019-1.494; p < .05). The metabolic signature mediated 35% of the total effect of HOMA-IR on AD-dementia risk. Significant metabolic pathways were related to glycerophospholipid and tyrosine metabolism. Conclusions We have identified a blood-based metabolic signature that reflects IR and may enhance our understanding of the biological mechanisms through which IR affects AD-dementia.
Àrees temàtiques: Aging; Biotecnología; Ciências ambientais; Ciências biológicas i; Ciências biológicas ii; Ciencias sociales; Educação física; General medicine; Geriatrics & gerontology; Geriatrics and gerontology; Gerontology; Interdisciplinar; Medicina i; Medicina ii; Medicina iii; Medicina veterinaria; Medicine (all); Nutrição; Odontología; Planejamento urbano e regional / demografia; Psychology; Saúde coletiva; Sociologia i política; Sociología y política
Accès a la llicència d'ús: https://creativecommons.org/licenses/by/3.0/es/
Adreça de correu electrònic de l'autor: jaume.folch@urv.cat; domenec.puig@urv.cat; monica.bullo@urv.cat; laia.gutierrez@iispv.cat; melina.rojas@estudiants.urv.cat; hatem.abdellatif@urv.cat; laura.panisello@urv.cat; javier.mateu@urv.cat; nil.novau@urv.cat; muhammad.mursil@urv.cat
Data d'alta del registre: 2026-02-13
Versió de l'article dipositat: info:eu-repo/semantics/publishedVersion
Referència a l'article segons font original: Journals Of Gerontology Series A-Biological Sciences And Medical Sciences. 80 (3): glae283-
Referència de l'ítem segons les normes APA: Gutierrez-Tordera, L; Panisello, L; García-Gonzalez, P; Ruiz, A; Cantero, JL; Rojas-Criollo, M; Mursil, M; Atienza, M; Novau-Ferré, N; Mateu-Fabregat, (2025). Metabolic Signature of Insulin Resistance and Risk of Alzheimer's Disease. Journals Of Gerontology Series A-Biological Sciences And Medical Sciences, 80(3), glae283-. DOI: 10.1093/gerona/glae283
URL Document de llicència: https://repositori.urv.cat/ca/proteccio-de-dades/
DOI de l'article: 10.1093/gerona/glae283
Entitat: Universitat Rovira i Virgili
Any de publicació de la revista: 2025-02-10
Tipus de publicació: Journal Publications
Repositori URV