Micropartículas, citocinas e leptina: possíveis biomarcadores do comprometimento cognitivo no envelhecimento?
Autor(a) principal: | |
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Data de Publicação: | 2017 |
Tipo de documento: | Tese |
Idioma: | por |
Título da fonte: | Repositório Institucional da UFMG |
Texto Completo: | http://hdl.handle.net/1843/33790 |
Resumo: | The clinical impairment established on Alzheimer’s Disease (AD) compromises the cognitive fuction, accompanied by personality and behavioral changes. On Mild Cognitive Impairment (MCI), the daily activities are preserved. In Subjective Cognitive Decline (SCD), there is a self-perceived decline, but without evidence of cognitive decline on standard neuropsychological tests. However, this condition may precede frequently the MCI and AD. Microparticles (MPs) are associated to cellular activation during inflammation, coagulation, vascular injuries and homeostasis. An inflammatory process is part of AD pathophysiology. And leptin has been demonstrated to have a neuroprotective role against AD pathology. This study aimed to investigate the MPs and cytokines levels, IL-1β, IL-6, TNF-α and IL-10; leptin and high sensitivity C Reactive protein (hsCRP) levels on patients with cognitive impairment (AD and MCI) and subjects with no objective cognitive impairment (SCD and controls). We evaluated platelets-derived MPs (PMPs), leukocytes-derived MPs (LMPs), tissue factor-derived MPs (TFMPs), endothelium-derived MPs (EMPs) and neuron-derived MPs (NMPs) levels in plasma, by flow cytometer assay. The cytokines and leptin levels were determined using enzyme linked immunosorbent assay (ELISA). And the hsCRP levels by immunoturbidimetric assay. We observed that TFMPs, LMPs and NMPs levels were significant increased, and IL-6, IL-1β, TNF-α and hsCRP were found to be significant lower in the AD group when compared to controls. The multiple logistic regression showed that TNF-α and NMPs were independently associated to AD, which resulted in a ROC curve with an area under the curve of 0.957 (sensitivity = 100% and specificity = 70%). Moreover we found higher MPs levels in sbjects with functional cognitive impairment and lower IL-6, IL1β, TNF-α and hsRCP and the functional and cognitive impairment, and lower levels of TNFα in subjects with no cognitive impairment. We found no difference in leptin levels between the cognitive impairment groups and SCD group. However, women demonstrated higher leptin serum levels than men. Higher leptin levels were observed in individuals ≥ 79 years old. The results suggest that MPs and TNF-α have a promising potential as biomarkers for AD diagnosis, but that leptin levels is not involved in the evolution for the cognitive impairment state but it is associated with inflammation, sex and age. |
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Micropartículas, citocinas e leptina: possíveis biomarcadores do comprometimento cognitivo no envelhecimento?Doença de AlzheimerComprometimento cognitivoBiomarcadoresMicropartículasCitocinasLeptinaThe clinical impairment established on Alzheimer’s Disease (AD) compromises the cognitive fuction, accompanied by personality and behavioral changes. On Mild Cognitive Impairment (MCI), the daily activities are preserved. In Subjective Cognitive Decline (SCD), there is a self-perceived decline, but without evidence of cognitive decline on standard neuropsychological tests. However, this condition may precede frequently the MCI and AD. Microparticles (MPs) are associated to cellular activation during inflammation, coagulation, vascular injuries and homeostasis. An inflammatory process is part of AD pathophysiology. And leptin has been demonstrated to have a neuroprotective role against AD pathology. This study aimed to investigate the MPs and cytokines levels, IL-1β, IL-6, TNF-α and IL-10; leptin and high sensitivity C Reactive protein (hsCRP) levels on patients with cognitive impairment (AD and MCI) and subjects with no objective cognitive impairment (SCD and controls). We evaluated platelets-derived MPs (PMPs), leukocytes-derived MPs (LMPs), tissue factor-derived MPs (TFMPs), endothelium-derived MPs (EMPs) and neuron-derived MPs (NMPs) levels in plasma, by flow cytometer assay. The cytokines and leptin levels were determined using enzyme linked immunosorbent assay (ELISA). And the hsCRP levels by immunoturbidimetric assay. We observed that TFMPs, LMPs and NMPs levels were significant increased, and IL-6, IL-1β, TNF-α and hsCRP were found to be significant lower in the AD group when compared to controls. The multiple logistic regression showed that TNF-α and NMPs were independently associated to AD, which resulted in a ROC curve with an area under the curve of 0.957 (sensitivity = 100% and specificity = 70%). Moreover we found higher MPs levels in sbjects with functional cognitive impairment and lower IL-6, IL1β, TNF-α and hsRCP and the functional and cognitive impairment, and lower levels of TNFα in subjects with no cognitive impairment. We found no difference in leptin levels between the cognitive impairment groups and SCD group. However, women demonstrated higher leptin serum levels than men. Higher leptin levels were observed in individuals ≥ 79 years old. The results suggest that MPs and TNF-α have a promising potential as biomarkers for AD diagnosis, but that leptin levels is not involved in the evolution for the cognitive impairment state but it is associated with inflammation, sex and age.As alterações clínicas decorrentes da Doença de Alzheimer (DA) afetam a função cognitiva do indivíduo, além de ocasionar mudanças na personalidade e comportamento. Já no comprometimento cognitivo leve (CCL), o indivíduo mantêm suas atividades cotidianas relativamente preservadas. No declínio cognitivo subjetivo (DCS), há um comprometimento auto-declarado, mas nenhuma evidência de declínio cognitivo em testes neuropsicológicos padrões. No entanto, esta condição pode preceder o CCL e a DA. As micropartículas (MPs) estão associadas à ativação celular durante a inflamação, coagulação, lesões vasculares e homeostase. O processo inflamatório faz parte da fisiopatologia da DA e a leptina, demonstrou um papel neuroprotetor contra a patologia da DA. Este estudo teve como objetivo investigar os níveis de MPs, das citocinas, IL-1β, IL-6, TNF-α e IL-10, de leptina e proteína C reativa ultrassensível (PCR-us), em pacientes com comprometimento cognitivo (DA e CCL) e indivíduos sem comprometimento cognitivo objetivo (DCS e controles). Avaliamos os níveis de MPs derivadas de plaquetas (PMPs), de leucócitos (LMPs), de fator tecidual (TFMPs), de endotélio (EMPs) e de neurônios (NMPs) no plasma por citometria de fluxo. As citocinas e a leptina foram determinadas no soro por ensaio de imunoenzimático (ELISA). E a PCR-us no soro por ensaio imunoturbidimétrico. Observamos que os níveis de TFMPs, LMPs e NMPs foram significativamente aumentados e a IL-6, IL-1β, TNF-α e PCR-us foram significativamente menores no grupo DA quando comparados aos controles. A regressão logística múltipla mostrou que TNF-α e NMPs foram associados independentemente com DA, o que resultou em uma curva ROC com área sob a curva de 0,957 (sensibilidade = 100% e especificidade = 70%). Além disso, encontramos níveis elevados de MPs em indivíduos com comprometimento funcional e cognitivo e níveis elevados de TNF-α em indivíduos sem comprometimento cognitivo. Não encontramos diferença significativa nos níveis de leptina entre os grupos. No entanto, as mulheres demonstraram níveis mais elevados de leptina do que os homens. E também foram observados níveis mais altos de leptina em indivíduos > 79 anos. Os resultados sugerem que MPs e TNF-α são biomarcadores potenciais para o diagnóstico de DA. E que os níveis de leptina não estão envolvidos na evolução para o estado de comprometimento cognitivo, mas está associado à inflamação ao sexo e a idadeUniversidade Federal de Minas GeraisBrasilFARMACIA - FACULDADE DE FARMACIAPrograma de Pós-Graduação em Análises Clínicas e ToxicológicasUFMGKarina Braga Gomes Borgeshttp://lattes.cnpq.br/0798429800100457Paulo CaramelliLirlândia Pires de SousaCarolina Antunes Magalhães2020-07-15T00:20:17Z2020-07-15T00:20:17Z2017-08-17info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesisapplication/pdfhttp://hdl.handle.net/1843/33790porhttp://creativecommons.org/licenses/by-nc-nd/3.0/pt/info:eu-repo/semantics/openAccessreponame:Repositório Institucional da UFMGinstname:Universidade Federal de Minas Gerais (UFMG)instacron:UFMG2020-07-15T00:20:17Zoai:repositorio.ufmg.br:1843/33790Repositório InstitucionalPUBhttps://repositorio.ufmg.br/oairepositorio@ufmg.bropendoar:2020-07-15T00:20:17Repositório Institucional da UFMG - Universidade Federal de Minas Gerais (UFMG)false |
dc.title.none.fl_str_mv |
Micropartículas, citocinas e leptina: possíveis biomarcadores do comprometimento cognitivo no envelhecimento? |
title |
Micropartículas, citocinas e leptina: possíveis biomarcadores do comprometimento cognitivo no envelhecimento? |
spellingShingle |
Micropartículas, citocinas e leptina: possíveis biomarcadores do comprometimento cognitivo no envelhecimento? Carolina Antunes Magalhães Doença de Alzheimer Comprometimento cognitivo Biomarcadores Micropartículas Citocinas Leptina |
title_short |
Micropartículas, citocinas e leptina: possíveis biomarcadores do comprometimento cognitivo no envelhecimento? |
title_full |
Micropartículas, citocinas e leptina: possíveis biomarcadores do comprometimento cognitivo no envelhecimento? |
title_fullStr |
Micropartículas, citocinas e leptina: possíveis biomarcadores do comprometimento cognitivo no envelhecimento? |
title_full_unstemmed |
Micropartículas, citocinas e leptina: possíveis biomarcadores do comprometimento cognitivo no envelhecimento? |
title_sort |
Micropartículas, citocinas e leptina: possíveis biomarcadores do comprometimento cognitivo no envelhecimento? |
author |
Carolina Antunes Magalhães |
author_facet |
Carolina Antunes Magalhães |
author_role |
author |
dc.contributor.none.fl_str_mv |
Karina Braga Gomes Borges http://lattes.cnpq.br/0798429800100457 Paulo Caramelli Lirlândia Pires de Sousa |
dc.contributor.author.fl_str_mv |
Carolina Antunes Magalhães |
dc.subject.por.fl_str_mv |
Doença de Alzheimer Comprometimento cognitivo Biomarcadores Micropartículas Citocinas Leptina |
topic |
Doença de Alzheimer Comprometimento cognitivo Biomarcadores Micropartículas Citocinas Leptina |
description |
The clinical impairment established on Alzheimer’s Disease (AD) compromises the cognitive fuction, accompanied by personality and behavioral changes. On Mild Cognitive Impairment (MCI), the daily activities are preserved. In Subjective Cognitive Decline (SCD), there is a self-perceived decline, but without evidence of cognitive decline on standard neuropsychological tests. However, this condition may precede frequently the MCI and AD. Microparticles (MPs) are associated to cellular activation during inflammation, coagulation, vascular injuries and homeostasis. An inflammatory process is part of AD pathophysiology. And leptin has been demonstrated to have a neuroprotective role against AD pathology. This study aimed to investigate the MPs and cytokines levels, IL-1β, IL-6, TNF-α and IL-10; leptin and high sensitivity C Reactive protein (hsCRP) levels on patients with cognitive impairment (AD and MCI) and subjects with no objective cognitive impairment (SCD and controls). We evaluated platelets-derived MPs (PMPs), leukocytes-derived MPs (LMPs), tissue factor-derived MPs (TFMPs), endothelium-derived MPs (EMPs) and neuron-derived MPs (NMPs) levels in plasma, by flow cytometer assay. The cytokines and leptin levels were determined using enzyme linked immunosorbent assay (ELISA). And the hsCRP levels by immunoturbidimetric assay. We observed that TFMPs, LMPs and NMPs levels were significant increased, and IL-6, IL-1β, TNF-α and hsCRP were found to be significant lower in the AD group when compared to controls. The multiple logistic regression showed that TNF-α and NMPs were independently associated to AD, which resulted in a ROC curve with an area under the curve of 0.957 (sensitivity = 100% and specificity = 70%). Moreover we found higher MPs levels in sbjects with functional cognitive impairment and lower IL-6, IL1β, TNF-α and hsRCP and the functional and cognitive impairment, and lower levels of TNFα in subjects with no cognitive impairment. We found no difference in leptin levels between the cognitive impairment groups and SCD group. However, women demonstrated higher leptin serum levels than men. Higher leptin levels were observed in individuals ≥ 79 years old. The results suggest that MPs and TNF-α have a promising potential as biomarkers for AD diagnosis, but that leptin levels is not involved in the evolution for the cognitive impairment state but it is associated with inflammation, sex and age. |
publishDate |
2017 |
dc.date.none.fl_str_mv |
2017-08-17 2020-07-15T00:20:17Z 2020-07-15T00:20:17Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/doctoralThesis |
format |
doctoralThesis |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/1843/33790 |
url |
http://hdl.handle.net/1843/33790 |
dc.language.iso.fl_str_mv |
por |
language |
por |
dc.rights.driver.fl_str_mv |
http://creativecommons.org/licenses/by-nc-nd/3.0/pt/ info:eu-repo/semantics/openAccess |
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http://creativecommons.org/licenses/by-nc-nd/3.0/pt/ |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.publisher.none.fl_str_mv |
Universidade Federal de Minas Gerais Brasil FARMACIA - FACULDADE DE FARMACIA Programa de Pós-Graduação em Análises Clínicas e Toxicológicas UFMG |
publisher.none.fl_str_mv |
Universidade Federal de Minas Gerais Brasil FARMACIA - FACULDADE DE FARMACIA Programa de Pós-Graduação em Análises Clínicas e Toxicológicas UFMG |
dc.source.none.fl_str_mv |
reponame:Repositório Institucional da UFMG instname:Universidade Federal de Minas Gerais (UFMG) instacron:UFMG |
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Universidade Federal de Minas Gerais (UFMG) |
instacron_str |
UFMG |
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UFMG |
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Repositório Institucional da UFMG |
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Repositório Institucional da UFMG |
repository.name.fl_str_mv |
Repositório Institucional da UFMG - Universidade Federal de Minas Gerais (UFMG) |
repository.mail.fl_str_mv |
repositorio@ufmg.br |
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1816829690096123904 |