RT Journal Article
T1 Plasma Concentrations of High Mobility Group Box 1 Proteins and Soluble Receptors for Advanced Glycation End-Products Are Relevant Biomarkers of Cognitive Impairment in Alcohol Use Disorder: A Pilot Study.
A1 Rodriguez-de-Fonseca, Fernando
A1 Medina-Paz, Francisco
A1 Sapozhnikov, Mira
A1 Hurtado-Guerrero, Isaac
A1 Rubio-Lamia, Leticia Olga
A1 Martín-de-las-Heras, Stella
A1 Requena-Ocaña, Nerea
A1 Flores-López, María
A1 Fernández-Arjona, María del Mar
A1 Rivera-González, Patricia
A1 Serrano, Antonia
A1 Serrano-Castro, Pedro Jesús
A1 Zapico, Sara C.
A1 Suárez-Pérez, Juan
K1 Plasma sanguíneo
K1 Alcohol - Consumo
AB Alcohol use disorder (AUD) is a major component in the etiology of cognitive decline and dementia. Underlying mechanisms by which long-term alcohol abuse causes cognitive dysfunction include excessive oxidative stress and inflammation in the brain, activated by increased reactive oxygen/nitrogen species (ROS/RNS), advanced glycation end-products (AGEs) and high-mobility group box 1 protein (HMGB1). In a pilot study, we examine the potential clinical value of circulating biomarkers of oxidative stress including ROS/RNS, HMGB1, the soluble receptor for AGE (sRAGE), the brain biomarker of aging apolipoprotein D (ApoD), and the antioxidant regulator nuclear factor erythroid 2-related factor 2 (NRF2) as predictive indices for cognitive impairment (CI) in abstinent patients with AUD (n = 25) compared to patients with established Alzheimer's disease (AD, n = 26) and control subjects (n = 25). Plasma concentrations of sRAGE were evaluated with immunoblotting; ROS/RNS with a fluorometric kit; and HMGB1, ApoD, and NRF2 by ELISA. Abstinent AUD patients had higher sRAGE, ROS/RNS (p < 0.05), and ApoD (p < 0.01) concentrations, similar to those of AD patients, and lower NRF2 (p < 0.01) concentrations, compared to controls. These changes were remarkable in AUD patients with CI. HMGB1, and sRAGE correlated positively with duration of alcohol use (rho = 0.398, p = 0.022; rho = 0.404, p = 0.018), whereas sRAGE correlated negatively with periods of alcohol abstinence (rho = -0.340, p = 0.045). A predictive model including ROS/RNS, HMGB1, sRAGE, alcohol use duration, and alcohol abstinence periods was able to differentiate AUD patients with CI (92.3% of correct predictions, ROC-AUC= 0.90) from those without CI. In conclusion, we propose ROS/RNS, HMGB1, and sRAGE as stress biomarkers capable of predicting cognitive impairment in AUD patients.
PB MDPI (Toxics)
YR 2024
FD 2024
LK https://hdl.handle.net/10630/33203
UL https://hdl.handle.net/10630/33203
LA eng
NO Rodríguez de Fonseca, F.; Medina-Paz, F.; Sapozhnikov, M.; Hurtado-Guerrero, I.; Rubio, L.; Martín-de-las-Heras, S.; RequenaOcaña, N.; Flores-López, M.; Fernández-Arjona, M.d.M.; Rivera, P.; et al. Plasma Concentrations of High Mobility Group Box 1 Proteins and Soluble Receptors for Advanced Glycation End-Products Are Relevant Biomarkers of Cognitive Impairment in Alcohol Use Disorder: A Pilot Study. Toxics 2024, 12, 190. https://doi.org/10.3390/toxics12030190
NO This research was funded by the Fulbright Visiting Scholar Program, United States Department of State and Ministerio de Educación y Formación Profesional (CAS21/00169, PRX21/00439); Instituto de Salud Carlos III (ISCIII), Ministerio de Ciencia e Innovación and European Regional Development Funds-European Union (ERDF-EU) (PI19/01577, PI20/01399). This study has been also funded by Instituto de Salud Carlos III (ISCIII) through the project “PI22/00427” and co-funded by the European Union. Additional funds come from Programa RICORS RIAPAD (RD21/0009/0003), Programa RETICS RTA (RD16/0017/000); Ministerio de Sanidad, Delegación de Gobierno para el Plan Nacional sobre Drogas (PNSD 2022/020, 2020/048, 2019/040); Consejería de Salud y Familia, Junta de Andalucía (Neuro-RECA, RIC-0111-2019); Consejería de Universidad, Investigación e Innovación, Junta de Andalucía (PI21/00291); Universidad de Málaga (B1-2022_35). I.H-G holds a “María Zambrano” research contract from the Ministry of Universities. P.R (CP19/00068) holds a “Miguel Servet I” research contract from the National System of Health, ERDF-EU-ISCIII.
DS RIUMA. Repositorio Institucional de la Universidad de Málaga
RD 20 ene 2026