Exosomal proteomes as a source for biomarker discovery in Alzheimer's disease

Detalhes bibliográficos
Autor(a) principal: Marçalo, Rui Filipe Santos
Data de Publicação: 2018
Tipo de documento: Dissertação
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10773/25180
Resumo: Exosomes are small extracellular vesicles (EVs) involved in various physiological and pathological processes. The potential of exosomes as biomarker resources for diagnostic, prognostic and even for therapeutics has intensified research in the field, supporting the potential of exosomes for biomarker discovery in several diseases, including in Alzheimer Disease (AD). This project had as main goal the identification of potential exosomal biomarker candidates in peripheral biofluids for Alzheimer’s Disease (AD). In order to do that, part of the study was to bioinformatically analyze exosomal proteomes of different peripheral biofluids, followed by a comparative study of the obtained results with an AD mimicking model. Additionally, serum samples from AD patients were analyzed by mass spectrometry (MS) and 87 potential biomarker candidates were identified. Of note, 3 proteins, IGVL1-51, IGVL2-11 and IGVL2-8, were identified exclusively in control samples, and 2 proteins, HIST1H4 and PRH1-2, were identified exclusively in AD samples. These 5 proteins may be potential exosomal biomarker candidates for AD diagnostic. Furthermore, 2 proteins, TF and KRT14, were found by both bioinformatic analysis and MS, although with ratios between 0.5 and 1, as decreased in AD. Interestingly, in this study, statistically significant differences in the size and concentration of AD exosomes were found, having AD exosomes a higher diameter but being decreased in concentration when compared to exosomes of Control samples. The identification of potential biomarker candidates for AD may be useful not only for early disease diagnosis but also to monitor disease progression, as well as for the development of new therapies for AD, which will translate in an improvement of patient’s life quality. Thus, with this study we propose a set of potential candidates for exosomal biomarkers for AD
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spelling Exosomal proteomes as a source for biomarker discovery in Alzheimer's diseaseAlzheimer’s diseaseBiomarkerExosomeMass spectrometryProteomeExosomes are small extracellular vesicles (EVs) involved in various physiological and pathological processes. The potential of exosomes as biomarker resources for diagnostic, prognostic and even for therapeutics has intensified research in the field, supporting the potential of exosomes for biomarker discovery in several diseases, including in Alzheimer Disease (AD). This project had as main goal the identification of potential exosomal biomarker candidates in peripheral biofluids for Alzheimer’s Disease (AD). In order to do that, part of the study was to bioinformatically analyze exosomal proteomes of different peripheral biofluids, followed by a comparative study of the obtained results with an AD mimicking model. Additionally, serum samples from AD patients were analyzed by mass spectrometry (MS) and 87 potential biomarker candidates were identified. Of note, 3 proteins, IGVL1-51, IGVL2-11 and IGVL2-8, were identified exclusively in control samples, and 2 proteins, HIST1H4 and PRH1-2, were identified exclusively in AD samples. These 5 proteins may be potential exosomal biomarker candidates for AD diagnostic. Furthermore, 2 proteins, TF and KRT14, were found by both bioinformatic analysis and MS, although with ratios between 0.5 and 1, as decreased in AD. Interestingly, in this study, statistically significant differences in the size and concentration of AD exosomes were found, having AD exosomes a higher diameter but being decreased in concentration when compared to exosomes of Control samples. The identification of potential biomarker candidates for AD may be useful not only for early disease diagnosis but also to monitor disease progression, as well as for the development of new therapies for AD, which will translate in an improvement of patient’s life quality. Thus, with this study we propose a set of potential candidates for exosomal biomarkers for ADOs exosomas são pequenas vesículas extracelulares envolvidas em vários processos fisiológicos e patológicos. O potencial dos exosomas como fontes de biomarcadores para o diagnóstico, prognóstico e mesmo para a terapêutica tem intensificado a investigação nesta área, apoiando o potencial dos exosomas na descoberta de biomarcadores, incluindo na doença de Alzheimer (AD). Este projeto teve como objetivo a identificação de potenciais biomarcadores exosomais, em biofluídos periféricos, para AD. Para tal, parte do estudo consistiu numa análise bioinformática dos proteomas de diferentes biofluídos periféricos, seguida de um estudo comparativo dos resultados obtidos com um modelo que mimetiza AD. Adicionalmente, amostras de soro de doentes com Alzheimer foram analisadas por espectrometria de massa (MS) e 87 potenciais candidatos a biomarcadores foram identificados. De realçar, 3 proteínas, IGVL1-51, IGVL2-11 e IGVL2-8, foram identificadas exclusivamente nos Controlos, e 2 proteínas, HIST1H4 e PRH1-2, foram identificadas exclusivamente nas amostras de AD. Estas 5 podem ser potenciais candidatos a biomarcadores exosomais para o diagnóstico de AD. Para além disso, 2 proteínas, TF e KRT14, foram ainda encontradas quer pela análise bioinformática quer por MS, embora com um ratio entre 0.5 e 1, como estando diminuídas em AD. Curiosamente, neste estudo foram encontradas diferenças estatísticas significativas no tamanho e concentração dos exosomas de amostras de AD, tendo os exosomas de AD maior diâmetro mas estando em menor concentração, em comparação com os exosomas de amostras controlo. A identificação de potenciais candidatos a biomarcadores para AD pode ser útil, não só no diagnóstico precoce da doença, como também para monitorizar a progressão e no desenvolvimento de terapias para AD, o que se traduzirá num impacto positivo na qualidade de vida do doente. Deste modo, com este estudo propomos um conjunto de potenciais candidatos a biomarcadores exosomais para a AD2021-01-07T00:00:00Z2018-12-19T00:00:00Z2018-12-19info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisapplication/pdfhttp://hdl.handle.net/10773/25180TID:202235351engMarçalo, Rui Filipe Santosinfo: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:RCAAP2024-02-22T11:49:03Zoai:ria.ua.pt:10773/25180Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-20T02:58:34.763209Repositório 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 Exosomal proteomes as a source for biomarker discovery in Alzheimer's disease
title Exosomal proteomes as a source for biomarker discovery in Alzheimer's disease
spellingShingle Exosomal proteomes as a source for biomarker discovery in Alzheimer's disease
Marçalo, Rui Filipe Santos
Alzheimer’s disease
Biomarker
Exosome
Mass spectrometry
Proteome
title_short Exosomal proteomes as a source for biomarker discovery in Alzheimer's disease
title_full Exosomal proteomes as a source for biomarker discovery in Alzheimer's disease
title_fullStr Exosomal proteomes as a source for biomarker discovery in Alzheimer's disease
title_full_unstemmed Exosomal proteomes as a source for biomarker discovery in Alzheimer's disease
title_sort Exosomal proteomes as a source for biomarker discovery in Alzheimer's disease
author Marçalo, Rui Filipe Santos
author_facet Marçalo, Rui Filipe Santos
author_role author
dc.contributor.author.fl_str_mv Marçalo, Rui Filipe Santos
dc.subject.por.fl_str_mv Alzheimer’s disease
Biomarker
Exosome
Mass spectrometry
Proteome
topic Alzheimer’s disease
Biomarker
Exosome
Mass spectrometry
Proteome
description Exosomes are small extracellular vesicles (EVs) involved in various physiological and pathological processes. The potential of exosomes as biomarker resources for diagnostic, prognostic and even for therapeutics has intensified research in the field, supporting the potential of exosomes for biomarker discovery in several diseases, including in Alzheimer Disease (AD). This project had as main goal the identification of potential exosomal biomarker candidates in peripheral biofluids for Alzheimer’s Disease (AD). In order to do that, part of the study was to bioinformatically analyze exosomal proteomes of different peripheral biofluids, followed by a comparative study of the obtained results with an AD mimicking model. Additionally, serum samples from AD patients were analyzed by mass spectrometry (MS) and 87 potential biomarker candidates were identified. Of note, 3 proteins, IGVL1-51, IGVL2-11 and IGVL2-8, were identified exclusively in control samples, and 2 proteins, HIST1H4 and PRH1-2, were identified exclusively in AD samples. These 5 proteins may be potential exosomal biomarker candidates for AD diagnostic. Furthermore, 2 proteins, TF and KRT14, were found by both bioinformatic analysis and MS, although with ratios between 0.5 and 1, as decreased in AD. Interestingly, in this study, statistically significant differences in the size and concentration of AD exosomes were found, having AD exosomes a higher diameter but being decreased in concentration when compared to exosomes of Control samples. The identification of potential biomarker candidates for AD may be useful not only for early disease diagnosis but also to monitor disease progression, as well as for the development of new therapies for AD, which will translate in an improvement of patient’s life quality. Thus, with this study we propose a set of potential candidates for exosomal biomarkers for AD
publishDate 2018
dc.date.none.fl_str_mv 2018-12-19T00:00:00Z
2018-12-19
2021-01-07T00:00:00Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/masterThesis
format masterThesis
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://hdl.handle.net/10773/25180
TID:202235351
url http://hdl.handle.net/10773/25180
identifier_str_mv TID:202235351
dc.language.iso.fl_str_mv eng
language eng
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dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron:RCAAP
instname_str Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
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