Blood levels of cytokines highlight the role of inflammation in Alzheimer's disease
Inflammation and angiogenesis have been defined as potential mechanisms associated with clinical progression from a cognitively normal state to Alzheimer's disease (AD). In this observational case-control study, we aimed to determine plasma levels of cytokines as indicators of inflammation involved in cognitive decline. We measured 30 plasma proteins in 49 controls (CTL), 36 individuals with mild cognitive impairment (MCI) and 52 patients diagnosed with probable AD. After applying strict filters for quantification limits, only 13 analytes were included in the analysis. Kruskal-Wallis tests showed significant differences between diagnostic groups for nine cytokines (IL-16, IL-7, VEGF, IL-8, eotaxin, MCP-1, MCP-4, MDC and TARC). Non-parametric MANCOVA showed that sex and diagnosis affected cytokine levels in the blood. To determine the sensitivity and specificity of the markers, we performed receiver operating characteristic (ROC) curve analysis. Only those analytes that showed an area under the curve (AUC) ≥ 0.70 were included in the multivariate logistic regression models to better understand the contribution of cytokines to clinical status. Three models: 1) CTL vs. AD; 2) CTL vs. MCI, and 3) MCI vs. AD were developed, with sex and age as covariates. In each model, two cytokines remained significantly different (model 1: IL-16 and MDC; model 2: eotaxin and MDC and model 3: IL-7 and VEGF). Taken together, this report identifies a set of plasma markers of inflammation and strengthens the role of glial biology in different clinical stages of AD.
Authors
- María Flores-López (ORCID: https://orcid.org/0000-0003-3489-1465)
- Lorenzo Campanelli
- Pedro Jesús Serrano-Castro (ORCID: https://orcid.org/0000-0002-3414-2707)
- Patricia Solís (ORCID: https://orcid.org/0000-0002-1058-5677)
- Fernando Rodrı́guez de Fonseca (ORCID: https://orcid.org/0000-0002-4516-5795)
- Julieta Lisso
- Juan Suárez (ORCID: https://orcid.org/0000-0001-5254-9802)
- Silvia Kochen (ORCID: https://orcid.org/0000-0003-0513-3534)
- Antonio J. López-Gambero (ORCID: https://orcid.org/0000-0001-7716-9056)
- Nicolás Irureta
- Laura Morelli (ORCID: https://orcid.org/0000-0001-5759-1807)
- Natividad Olivar (ORCID: https://orcid.org/0000-0003-4598-6865)
- Daniel Gustavo Politis (ORCID: https://orcid.org/0000-0002-9964-0272)
- Ivana Yoseli Quiroga (ORCID: https://orcid.org/0000-0002-6799-0059)
- Luis Ignacio Brusco
- Nerea Requena-Ocaña (ORCID: https://orcid.org/0000-0003-3257-8459)
- Gisela V. Novack (ORCID: https://orcid.org/0000-0003-0574-292X)
- Ivana Villella (ORCID: https://orcid.org/0009-0009-3212-9654)
- Nancy Medel
- José Antonio Reyes-Bueno (ORCID: https://orcid.org/0000-0002-9117-9426)
- Pablo Galeano (ORCID: https://orcid.org/0000-0003-4491-2039)
- Fernando Taragano
- Nancy Wukitsevits
- Claudia Kairiyama
- Federico Ariel Prestia
- Carolina Muchnik
- Inés Mintz (ORCID: https://orcid.org/0009-0007-8735-036X)
- Zulma Sevillano
- Carolina Dalmasso (ORCID: https://orcid.org/0000-0002-4901-9955)
- Cristian Gona
- Karen S. Campuzano
- Eduardo M. Castaño
- Carolina De La Cuesta
Institutions
- Universidad de Buenos Aires (AR)
- Fundación Instituto Leloir (AR)
- Universidad Nacional Arturo Jauretche (AR)
- Hospital Regional Universitario de Málaga (ES)
- Hospital El Cruce (AR)
- Andalusian Centre for Nanomedicine and Biotechnology (ES)
- National University of the Arts (AR)
- Hospital General de Niños Ricardo Gutierrez (AR)
- Universidad de Málaga (ES)
Publication Details
- Journal
- Heliyon
- Published
- 2025-01-01
- DOI
- https://doi.org/10.1016/j.heliyon.2025.e41725
- Citations
- 6
- Primary Topic
- Tryptophan and brain disorders
- Type
- article
- Field-Weighted Citation Impact
- 3.47
Funders
- European Commission
- Consejo Nacional de Investigaciones Científicas y Técnicas
- Universidad Nacional del Litoral
- Universität zu Köln
- Plan Nacional sobre Drogas
- Agencia Nacional de Promoción Científica y Tecnológica
- Instituto de Salud Carlos III
- Fondo para la Investigación Científica y Tecnológica