Inflammatory biomarkers in Alzheimer’s disease

Detalhes bibliográficos
Autor(a) principal: Barra, Cátia Isabel de Almeida
Data de Publicação: 2014
Tipo de documento: Dissertação
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10773/13277
Resumo: Alzheimer’s disease (AD) is the most common form of dementia. Histopathologically it is characterized by the presence of two major hallmarks, the intracellular neurofibrillary tangles (NFT) and the extracellular senile plaques (SP), which are surrounded by activated astrocytes and microglia. Neuroinflammation has been associated with some neurodegenerative diseases. In AD the inflammatory process, prompted by increased Aβ production and aggregation, was reported to have a fundamental role in disease pathogenesis. In early stages the inflammation could have a beneficial role in the pathology, since it has been proposed that the microglia and astrocytes activated could be involved in (amyloid β) Aβ clearance. Nevertheless, the chronic activation of the microglia leads to excessive production of the inflammatory components, including cytokines. It promotes alterations in amyloid precursor protein (APP) expression and processing, stimulating the increase of Aβ accumulation, abnormal Tau phosphorylation and, consequently, neurotoxic effects, irreversible damage and loss of neurons. Since chronic neuroinflammation is a feature of AD, inflammatory proteins may constitute potential biomarkers candidates to assist clinical diagnosis of this dementia. Thus, the main aim of this study was to identify putative inflammatory biomarkers for AD by flow citometry analysis. For plasma samples of individuals examined by clinical dementia rating (CDR) and mini mental (MM) diagnostic tests were used. Subjects were subdivided in 3 distinct groups, a control group (CDR-/MM-) and two patient groups, CDR+/MM- and CRD+/MM+, the former may include mild cognitive impairment (MCI) patients and the latest group included 5 patients clinical diagnosed as AD. Data analysis revealed differences in the inflammatory proteins levels of both patients groups (CDR+/MM- and CDR+/MM+) in comparison to healthy individuals (CDR-/MM-). Interleukin-8 (IL-8) plasma levels were statistically different (P<0,05) from control group. Significant correlation between IL-8 concentrations and the CDR stages was also identified. Additionally, correlations of monocyte chemoattractant protein-1 (MCP-1) with both IL-8 and IL-6 were observed. Taken together these findings suggested that IL-8 could be a potential biomarker not only for AD but also for diagnosis of initial stages of dementia.
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spelling Inflammatory biomarkers in Alzheimer’s diseaseBiomedicinaDoença de AlzheimerMarcadores bioquímicosCitocininasAlzheimer’s disease (AD) is the most common form of dementia. Histopathologically it is characterized by the presence of two major hallmarks, the intracellular neurofibrillary tangles (NFT) and the extracellular senile plaques (SP), which are surrounded by activated astrocytes and microglia. Neuroinflammation has been associated with some neurodegenerative diseases. In AD the inflammatory process, prompted by increased Aβ production and aggregation, was reported to have a fundamental role in disease pathogenesis. In early stages the inflammation could have a beneficial role in the pathology, since it has been proposed that the microglia and astrocytes activated could be involved in (amyloid β) Aβ clearance. Nevertheless, the chronic activation of the microglia leads to excessive production of the inflammatory components, including cytokines. It promotes alterations in amyloid precursor protein (APP) expression and processing, stimulating the increase of Aβ accumulation, abnormal Tau phosphorylation and, consequently, neurotoxic effects, irreversible damage and loss of neurons. Since chronic neuroinflammation is a feature of AD, inflammatory proteins may constitute potential biomarkers candidates to assist clinical diagnosis of this dementia. Thus, the main aim of this study was to identify putative inflammatory biomarkers for AD by flow citometry analysis. For plasma samples of individuals examined by clinical dementia rating (CDR) and mini mental (MM) diagnostic tests were used. Subjects were subdivided in 3 distinct groups, a control group (CDR-/MM-) and two patient groups, CDR+/MM- and CRD+/MM+, the former may include mild cognitive impairment (MCI) patients and the latest group included 5 patients clinical diagnosed as AD. Data analysis revealed differences in the inflammatory proteins levels of both patients groups (CDR+/MM- and CDR+/MM+) in comparison to healthy individuals (CDR-/MM-). Interleukin-8 (IL-8) plasma levels were statistically different (P<0,05) from control group. Significant correlation between IL-8 concentrations and the CDR stages was also identified. Additionally, correlations of monocyte chemoattractant protein-1 (MCP-1) with both IL-8 and IL-6 were observed. Taken together these findings suggested that IL-8 could be a potential biomarker not only for AD but also for diagnosis of initial stages of dementia.A doença de Alzheimer (DA) é o tipo de demência mais comum. Histopatologicamente é caracterizada pela presença de tranças neurofibrilares intracelulares (TNF) e de placas senis extracelulares (PS), as quais estão rodeadas pela microglia e por astrócitos. A neuroinflamação tem sido associada com várias doenças neurodegenerativas. Na DA o processo inflamatório, desencadeado pelo aumento da produção e agregação do péptido Aβ, desempenha um papel fundamental na patogénese da doença. Nas fases inicias, a inflamação possui um papel benéfico na patologia, uma vez que tem sido proposto que a microglia e os astrócitos quando ativados estão envolvidos na remoção de β-amilóide (Aβ). No entanto, a ativação crónica da microglia conduz à produção excessiva de componentes inflamatórios, incluindo citocinas. Isto provoca alterações na expressão e processamento da proteína percursora de amilóide (PPA), estimulando o aumento da produção e acumulação de Aβ, fosforilação anormal da proteína Tau e, consequentemente, efeitos neurotóxicos e perda de neurónios. Uma vez que a neuroinflamação crónica é uma característica da DA, proteínas inflamatórias poderão constituir potenciais candidatos a biomarcadores que auxiliem no diagnóstico clínico desta doença. Desta forma, o principal objectivo deste trabalho foi identificar biomarcadores inflamatórios para a DA através da técnica de citometria de fluxo. Para tal, foram analisadas amostras de plasma de doentes que foram, previamente, examinados por testes de avaliação cognitiva, clinical dementia rating (CDR) e mini mental (MM). Os sujeitos foram divididos em três grupos distintos, o grupo controlo (CDR-/MM-) e dois grupos de pacientes, CDR+/MM- e CDR+/MM+. O primeiro grupo de pacientes pode conter indivíduos com ligeiras alterações cognitivas (MCI) e o segundo inclui 5 pacientes clinicamente diagnosticados para DA. A análise dos dados revelou diferenças nos níveis de proteínas inflamatórias de ambos os grupos de doentes (CDR+/MM- e CDR+/MM+) em comparação com os indivíduos saudáveis (CDR-/MM-). Os níveis plasmáticos de interleucina-8 (IL-8) foram estatisticamente deferentes (p<0,05) do grupo controlo. Correlação significativa entre as concentrações de IL-8 e os estados de CDR foi identificada. Adicionalmente, foram observadas correlações entre MCP-1 e IL-8 e a IL-6. Em conjunto, estes resultados sugerem que a IL-8 poderá ser um potencial biomarcador não só para a DA mas também para o diagnóstico precoce de demência.Universidade de Aveiro2018-07-20T14:00:47Z2016-07-10T00:00:00Z2014-01-01T00:00:00Z2014info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisapplication/pdfhttp://hdl.handle.net/10773/13277TID:201569892engBarra, Cátia Isabel de Almeidainfo:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2024-02-22T11:24:06Zoai:ria.ua.pt:10773/13277Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-20T02:49:09.233994Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse
dc.title.none.fl_str_mv Inflammatory biomarkers in Alzheimer’s disease
title Inflammatory biomarkers in Alzheimer’s disease
spellingShingle Inflammatory biomarkers in Alzheimer’s disease
Barra, Cátia Isabel de Almeida
Biomedicina
Doença de Alzheimer
Marcadores bioquímicos
Citocininas
title_short Inflammatory biomarkers in Alzheimer’s disease
title_full Inflammatory biomarkers in Alzheimer’s disease
title_fullStr Inflammatory biomarkers in Alzheimer’s disease
title_full_unstemmed Inflammatory biomarkers in Alzheimer’s disease
title_sort Inflammatory biomarkers in Alzheimer’s disease
author Barra, Cátia Isabel de Almeida
author_facet Barra, Cátia Isabel de Almeida
author_role author
dc.contributor.author.fl_str_mv Barra, Cátia Isabel de Almeida
dc.subject.por.fl_str_mv Biomedicina
Doença de Alzheimer
Marcadores bioquímicos
Citocininas
topic Biomedicina
Doença de Alzheimer
Marcadores bioquímicos
Citocininas
description Alzheimer’s disease (AD) is the most common form of dementia. Histopathologically it is characterized by the presence of two major hallmarks, the intracellular neurofibrillary tangles (NFT) and the extracellular senile plaques (SP), which are surrounded by activated astrocytes and microglia. Neuroinflammation has been associated with some neurodegenerative diseases. In AD the inflammatory process, prompted by increased Aβ production and aggregation, was reported to have a fundamental role in disease pathogenesis. In early stages the inflammation could have a beneficial role in the pathology, since it has been proposed that the microglia and astrocytes activated could be involved in (amyloid β) Aβ clearance. Nevertheless, the chronic activation of the microglia leads to excessive production of the inflammatory components, including cytokines. It promotes alterations in amyloid precursor protein (APP) expression and processing, stimulating the increase of Aβ accumulation, abnormal Tau phosphorylation and, consequently, neurotoxic effects, irreversible damage and loss of neurons. Since chronic neuroinflammation is a feature of AD, inflammatory proteins may constitute potential biomarkers candidates to assist clinical diagnosis of this dementia. Thus, the main aim of this study was to identify putative inflammatory biomarkers for AD by flow citometry analysis. For plasma samples of individuals examined by clinical dementia rating (CDR) and mini mental (MM) diagnostic tests were used. Subjects were subdivided in 3 distinct groups, a control group (CDR-/MM-) and two patient groups, CDR+/MM- and CRD+/MM+, the former may include mild cognitive impairment (MCI) patients and the latest group included 5 patients clinical diagnosed as AD. Data analysis revealed differences in the inflammatory proteins levels of both patients groups (CDR+/MM- and CDR+/MM+) in comparison to healthy individuals (CDR-/MM-). Interleukin-8 (IL-8) plasma levels were statistically different (P<0,05) from control group. Significant correlation between IL-8 concentrations and the CDR stages was also identified. Additionally, correlations of monocyte chemoattractant protein-1 (MCP-1) with both IL-8 and IL-6 were observed. Taken together these findings suggested that IL-8 could be a potential biomarker not only for AD but also for diagnosis of initial stages of dementia.
publishDate 2014
dc.date.none.fl_str_mv 2014-01-01T00:00:00Z
2014
2016-07-10T00:00:00Z
2018-07-20T14:00:47Z
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