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 invo...

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Main Authors: Lorenzo Campanelli, Pablo Galeano, Federico A. Prestia, Carolina Cuesta, Maria C. Dalmasso, María Flores-López, Cristian Gona, Nicolás Irureta, Claudia Kairiyama, Julieta Lisso, Antonio Jesús López-Gambero, Ines Mintz, Nancy Medel, Karen S. Campuzano, Carolina Muchnik, Gisela V. Novack, Natividad Olivar, Ivana Quiroga, Nerea Requena-Ocaña, Jose Antonio Reyes-Bueno, Pedro Serrano-Castro, Zulma Sevillano, Patricia Solis, Juan Suárez, Ivana Villella, Nancy Wukitsevits, Eduardo M. Castaño, Fernando Taragano, Silvia Kochen, Daniel G. Politis, Luis I. Brusco, Fernando Rodríguez de Fonseca, Laura Morelli
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Language:English
Published: Elsevier 2025-01-01
Series:Heliyon
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Online Access:http://www.sciencedirect.com/science/article/pii/S2405844025001057
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author Lorenzo Campanelli
Pablo Galeano
Federico A. Prestia
Carolina Cuesta
Maria C. Dalmasso
María Flores-López
Cristian Gona
Nicolás Irureta
Claudia Kairiyama
Julieta Lisso
Antonio Jesús López-Gambero
Ines Mintz
Nancy Medel
Karen S. Campuzano
Carolina Muchnik
Gisela V. Novack
Natividad Olivar
Ivana Quiroga
Nerea Requena-Ocaña
Jose Antonio Reyes-Bueno
Pedro Serrano-Castro
Zulma Sevillano
Patricia Solis
Juan Suárez
Ivana Villella
Nancy Wukitsevits
Eduardo M. Castaño
Fernando Taragano
Silvia Kochen
Daniel G. Politis
Luis I. Brusco
Fernando Rodríguez de Fonseca
Laura Morelli
author_facet Lorenzo Campanelli
Pablo Galeano
Federico A. Prestia
Carolina Cuesta
Maria C. Dalmasso
María Flores-López
Cristian Gona
Nicolás Irureta
Claudia Kairiyama
Julieta Lisso
Antonio Jesús López-Gambero
Ines Mintz
Nancy Medel
Karen S. Campuzano
Carolina Muchnik
Gisela V. Novack
Natividad Olivar
Ivana Quiroga
Nerea Requena-Ocaña
Jose Antonio Reyes-Bueno
Pedro Serrano-Castro
Zulma Sevillano
Patricia Solis
Juan Suárez
Ivana Villella
Nancy Wukitsevits
Eduardo M. Castaño
Fernando Taragano
Silvia Kochen
Daniel G. Politis
Luis I. Brusco
Fernando Rodríguez de Fonseca
Laura Morelli
author_sort Lorenzo Campanelli
collection DOAJ
description 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.
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spelling doaj-art-6ee8549a8b3a4e1fbcccf36f2bb6390f2025-02-02T05:28:02ZengElsevierHeliyon2405-84402025-01-01112e41725Blood levels of cytokines highlight the role of inflammation in Alzheimer's diseaseLorenzo Campanelli0Pablo Galeano1Federico A. Prestia2Carolina Cuesta3Maria C. Dalmasso4María Flores-López5Cristian Gona6Nicolás Irureta7Claudia Kairiyama8Julieta Lisso9Antonio Jesús López-Gambero10Ines Mintz11Nancy Medel12Karen S. Campuzano13Carolina Muchnik14Gisela V. Novack15Natividad Olivar16Ivana Quiroga17Nerea Requena-Ocaña18Jose Antonio Reyes-Bueno19Pedro Serrano-Castro20Zulma Sevillano21Patricia Solis22Juan Suárez23Ivana Villella24Nancy Wukitsevits25Eduardo M. Castaño26Fernando Taragano27Silvia Kochen28Daniel G. Politis29Luis I. Brusco30Fernando Rodríguez de Fonseca31Laura Morelli32Laboratory of Brain Aging and Neurodegeneration, Fundación Instituto Leloir, IIBBA-CONICET, Av. Patricias Argentinas 435, Ciudad Autónoma de Buenos Aires, ArgentinaLaboratory of Brain Aging and Neurodegeneration, Fundación Instituto Leloir, IIBBA-CONICET, Av. Patricias Argentinas 435, Ciudad Autónoma de Buenos Aires, ArgentinaLaboratory of Brain Aging and Neurodegeneration, Fundación Instituto Leloir, IIBBA-CONICET, Av. Patricias Argentinas 435, Ciudad Autónoma de Buenos Aires, ArgentinaHospital Interzonal General de Agudos (HIGA) Eva Perón, Av. 101 Dr. Ricardo Balbín 3200, Provincia de Buenos Aires, Buenos Aires, B1650NBN, ArgentinaStudies in Neuroscience and Complex Systems Unit (CONICET-HEC-UNAJ), Av. Calchaquí 5402, Florencio Varela, ArgentinaGrupo de Neuropsicofarmacología, IBIMA-Plataforma BIONAND, Hospital Regional Universitario de Málaga, Puerto de la Torre, 29010, Málaga, Spain; Unidad de Gestión Clínica de Salud Mental, IBIMA-Plataforma BIONAND, Hospital Regional Universitario de Málaga, Málaga, Spain, Puerto de la Torre, 29010, Málaga, SpainAsistencia Medica Integral, Hospital El Cruce, Av. Calchaquí 5401, Provincia de Buenos Aires, Florencio Varela, ArgentinaStudies in Neuroscience and Complex Systems Unit (CONICET-HEC-UNAJ), Av. Calchaquí 5402, Florencio Varela, Argentina; Asistencia Medica Integral, Hospital El Cruce, Av. Calchaquí 5401, Provincia de Buenos Aires, Florencio Varela, ArgentinaHospital Interzonal General de Agudos (HIGA) Eva Perón, Av. 101 Dr. Ricardo Balbín 3200, Provincia de Buenos Aires, Buenos Aires, B1650NBN, ArgentinaStudies in Neuroscience and Complex Systems Unit (CONICET-HEC-UNAJ), Av. Calchaquí 5402, Florencio Varela, Argentina; Asistencia Medica Integral, Hospital El Cruce, Av. Calchaquí 5401, Provincia de Buenos Aires, Florencio Varela, ArgentinaGrupo de Neuropsicofarmacología, IBIMA-Plataforma BIONAND, Hospital Regional Universitario de Málaga, Puerto de la Torre, 29010, Málaga, Spain; Unidad de Gestión Clínica de Salud Mental, IBIMA-Plataforma BIONAND, Hospital Regional Universitario de Málaga, Málaga, Spain, Puerto de la Torre, 29010, Málaga, SpainStudies in Neuroscience and Complex Systems Unit (CONICET-HEC-UNAJ), Av. Calchaquí 5402, Florencio Varela, Argentina; Asistencia Medica Integral, Hospital El Cruce, Av. Calchaquí 5401, Provincia de Buenos Aires, Florencio Varela, ArgentinaStudies in Neuroscience and Complex Systems Unit (CONICET-HEC-UNAJ), Av. Calchaquí 5402, Florencio Varela, Argentina; Asistencia Medica Integral, Hospital El Cruce, Av. Calchaquí 5401, Provincia de Buenos Aires, Florencio Varela, ArgentinaLaboratory of Brain Aging and Neurodegeneration, Fundación Instituto Leloir, IIBBA-CONICET, Av. Patricias Argentinas 435, Ciudad Autónoma de Buenos Aires, ArgentinaCenter of Neuropsychiatry and Behavior Neurology, School of Medicine, University of Buenos Aires, Paraguay 2155, Ciudad Autónoma de Buenos Aires, ArgentinaLaboratory of Brain Aging and Neurodegeneration, Fundación Instituto Leloir, IIBBA-CONICET, Av. Patricias Argentinas 435, Ciudad Autónoma de Buenos Aires, ArgentinaCenter of Neuropsychiatry and Behavior Neurology, School of Medicine, University of Buenos Aires, Paraguay 2155, Ciudad Autónoma de Buenos Aires, ArgentinaAsistencia Medica Integral, Hospital El Cruce, Av. Calchaquí 5401, Provincia de Buenos Aires, Florencio Varela, ArgentinaGrupo de Neuropsicofarmacología, IBIMA-Plataforma BIONAND, Hospital Regional Universitario de Málaga, Puerto de la Torre, 29010, Málaga, Spain; Unidad de Gestión Clínica de Salud Mental, IBIMA-Plataforma BIONAND, Hospital Regional Universitario de Málaga, Málaga, Spain, Puerto de la Torre, 29010, Málaga, SpainUnidad de Neurología, IBIMA-Plataforma BIONAND, Hospital Regional Universitario de Málaga, Malaga, Puerto de la Torre, 29010, Málaga, Spain; Andalusian Network for Clinical and Translational Research in Neurology [NEURO-RECA], Av. Carlos Haya, 88, Pabellon B, 4a planta, 29010, Málaga, SpainUnidad de Neurología, IBIMA-Plataforma BIONAND, Hospital Regional Universitario de Málaga, Malaga, Puerto de la Torre, 29010, Málaga, Spain; Andalusian Network for Clinical and Translational Research in Neurology [NEURO-RECA], Av. Carlos Haya, 88, Pabellon B, 4a planta, 29010, Málaga, SpainStudies in Neuroscience and Complex Systems Unit (CONICET-HEC-UNAJ), Av. Calchaquí 5402, Florencio Varela, Argentina; Asistencia Medica Integral, Hospital El Cruce, Av. Calchaquí 5401, Provincia de Buenos Aires, Florencio Varela, ArgentinaStudies in Neuroscience and Complex Systems Unit (CONICET-HEC-UNAJ), Av. Calchaquí 5402, Florencio Varela, Argentina; Asistencia Medica Integral, Hospital El Cruce, Av. Calchaquí 5401, Provincia de Buenos Aires, Florencio Varela, ArgentinaGrupo de Neuropsicofarmacología, IBIMA-Plataforma BIONAND, Hospital Regional Universitario de Málaga, Puerto de la Torre, 29010, Málaga, Spain; Andalusian Network for Clinical and Translational Research in Neurology [NEURO-RECA], Av. Carlos Haya, 88, Pabellon B, 4a planta, 29010, Málaga, Spain; Departamento of Anatomía Humana, Medicina Legal e Historia de la Ciencia, Facultad de Medicina, Universidad de Málaga, Av. Cervantes, 2, 2907, Málaga, SpainStudies in Neuroscience and Complex Systems Unit (CONICET-HEC-UNAJ), Av. Calchaquí 5402, Florencio Varela, Argentina; Asistencia Medica Integral, Hospital El Cruce, Av. Calchaquí 5401, Provincia de Buenos Aires, Florencio Varela, ArgentinaAsistencia Medica Integral, Hospital El Cruce, Av. Calchaquí 5401, Provincia de Buenos Aires, Florencio Varela, ArgentinaLaboratory of Brain Aging and Neurodegeneration, Fundación Instituto Leloir, IIBBA-CONICET, Av. Patricias Argentinas 435, Ciudad Autónoma de Buenos Aires, ArgentinaNeuropsychiatric Clinic Nuestra Señora de Las Nieves, Av. Álvarez Thomas 268, C1427CCP, Ciudad Autónoma de Buenos Aires, ArgentinaStudies in Neuroscience and Complex Systems Unit (CONICET-HEC-UNAJ), Av. Calchaquí 5402, Florencio Varela, ArgentinaHospital Interzonal General de Agudos (HIGA) Eva Perón, Av. 101 Dr. Ricardo Balbín 3200, Provincia de Buenos Aires, Buenos Aires, B1650NBN, ArgentinaCenter of Neuropsychiatry and Behavior Neurology, School of Medicine, University of Buenos Aires, Paraguay 2155, Ciudad Autónoma de Buenos Aires, ArgentinaGrupo de Neuropsicofarmacología, IBIMA-Plataforma BIONAND, Hospital Regional Universitario de Málaga, Puerto de la Torre, 29010, Málaga, Spain; Unidad de Gestión Clínica de Salud Mental, IBIMA-Plataforma BIONAND, Hospital Regional Universitario de Málaga, Málaga, Spain, Puerto de la Torre, 29010, Málaga, Spain; Unidad de Neurología, IBIMA-Plataforma BIONAND, Hospital Regional Universitario de Málaga, Malaga, Puerto de la Torre, 29010, Málaga, Spain; Andalusian Network for Clinical and Translational Research in Neurology [NEURO-RECA], Av. Carlos Haya, 88, Pabellon B, 4a planta, 29010, Málaga, SpainLaboratory of Brain Aging and Neurodegeneration, Fundación Instituto Leloir, IIBBA-CONICET, Av. Patricias Argentinas 435, Ciudad Autónoma de Buenos Aires, Argentina; Corresponding author. Laboratory of Brain Aging and Neurodegeneration, Fundación Instituto Leloir (IIBBA-CONICET), Av. Patricias Argentinas 435, 1405, Buenos Aires, Argentina.lmorelli@leloir.org.arInflammation 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.http://www.sciencedirect.com/science/article/pii/S2405844025001057DementiaGlial cellsPlasmaInflammationInterleukinsChemoattractants
spellingShingle Lorenzo Campanelli
Pablo Galeano
Federico A. Prestia
Carolina Cuesta
Maria C. Dalmasso
María Flores-López
Cristian Gona
Nicolás Irureta
Claudia Kairiyama
Julieta Lisso
Antonio Jesús López-Gambero
Ines Mintz
Nancy Medel
Karen S. Campuzano
Carolina Muchnik
Gisela V. Novack
Natividad Olivar
Ivana Quiroga
Nerea Requena-Ocaña
Jose Antonio Reyes-Bueno
Pedro Serrano-Castro
Zulma Sevillano
Patricia Solis
Juan Suárez
Ivana Villella
Nancy Wukitsevits
Eduardo M. Castaño
Fernando Taragano
Silvia Kochen
Daniel G. Politis
Luis I. Brusco
Fernando Rodríguez de Fonseca
Laura Morelli
Blood levels of cytokines highlight the role of inflammation in Alzheimer's disease
Heliyon
Dementia
Glial cells
Plasma
Inflammation
Interleukins
Chemoattractants
title Blood levels of cytokines highlight the role of inflammation in Alzheimer's disease
title_full Blood levels of cytokines highlight the role of inflammation in Alzheimer's disease
title_fullStr Blood levels of cytokines highlight the role of inflammation in Alzheimer's disease
title_full_unstemmed Blood levels of cytokines highlight the role of inflammation in Alzheimer's disease
title_short Blood levels of cytokines highlight the role of inflammation in Alzheimer's disease
title_sort blood levels of cytokines highlight the role of inflammation in alzheimer s disease
topic Dementia
Glial cells
Plasma
Inflammation
Interleukins
Chemoattractants
url http://www.sciencedirect.com/science/article/pii/S2405844025001057
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