ADAM10 como biomarcadora de Transtorno Neurocognitivo Leve

Detalhes bibliográficos
Autor(a) principal: Vatanabe, Izabela Pereira
Data de Publicação: 2020
Tipo de documento: Tese
Idioma: por
Título da fonte: Repositório Institucional da UFSCAR
Texto Completo: https://repositorio.ufscar.br/handle/ufscar/13363
Resumo: Mild cognitive impairment (MCI), in the absence of dementia, and associated with physical frailty gave rise to the new concept called cognitive frailty. This new concept has also been considered as a subtype of frailty. Moreover, along with the aging process and its interaction with physical frailty, it accelerates the cycle of functional decline and results in poor quality of life and other negative outcomes in older adults. Previous studies have suggested that MCI may represent a condition that predates Alzheimer's disease (AD), based on the high conversion rate for it. With that in mind, the principal aim of this study was to evaluate whether the platelet and plasma levels of ADAM10 could act as biomarkers of the concomitant conditions of MCI and physical frailty, in order to support the new construct of cognitive frailty. The study was carried out with a population aged over 60 years old who were in the coverage of a family health center in the city of São Carlos-SP, Brazil. The subjects were properly assessed for cognition and physical frailty. Subsequently, biological samples were collected, analyzed and stored in a biorepository. The levels of platelet and plasma ADAM10 were analyzed using the Western blot technique in subjects with MCI, compared to subjects without the presence of cognitive impairments, both with and without the presence of frailty. The results indicate that ADAM10 levels are reduced in platelets and increased in plasma of older adults with MCI when compared to healthy controls, regardless of the condition of physical frailty. Based on the results obtained, this study raised the hypothesis that the plasma and soluble form of ADAM10 would be inactive, whereas the platelet form, anchored to the cell plasma membrane, would be active. Thus, we also aimed to assess whether the enzymatic activity of ADAM10 is dependent on its anchoring to the plasma membrane through the evaluation of the enzymatic activity of ADAM10 after the isolation of different fractions of SH-SY5Y neuroblastoma cells. Due to the worldwide pandemic scenario, the enzyme activity assay in cell fractions could not be completed, however a previous study carried out by this research group proved that ADAM10 found in plasma is enzymatically inactive, whereas the platelet form of the protein, was shown to be active, confirming our hypothesis that the reduced levels of active ADAM10 (60 kDa) are related to the condition of MCI, as well as the increased levels of inactive ADAM10 (50 kDa). Taken together, the results demonstrate that ADAM10 cannot be considered as a biomarker in conditions of cognitive frailty, but can act effectively as a low-cost, easy-access and low-invasive biomarker molecule for MCI. These results contribute to a better understanding of the biology of the molecule, as well as for the implantation of tools that promote the diagnosis of MCI. Furthermore, the evidence may guide the health teams to a more adequate planning, with the purpose of improving the quality of life of the older adults affected by this condition, and to direct therapeutic strategies and the prevention of injuries.
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spelling Vatanabe, Izabela PereiraCominetti, Márcia Reginahttp://lattes.cnpq.br/3725318894555272Manzine, Patricia Reginahttp://lattes.cnpq.br/6348503930553992http://lattes.cnpq.br/35465529311586439eb5cd72-a42c-4864-bdb8-cd40bb4c57512020-10-22T17:37:04Z2020-10-22T17:37:04Z2020-09-28VATANABE, Izabela Pereira. ADAM10 como biomarcadora de Transtorno Neurocognitivo Leve. 2020. Tese (Doutorado em Ciências Fisiológicas) – Universidade Federal de São Carlos, São Carlos, 2020. Disponível em: https://repositorio.ufscar.br/handle/ufscar/13363.https://repositorio.ufscar.br/handle/ufscar/13363Mild cognitive impairment (MCI), in the absence of dementia, and associated with physical frailty gave rise to the new concept called cognitive frailty. This new concept has also been considered as a subtype of frailty. Moreover, along with the aging process and its interaction with physical frailty, it accelerates the cycle of functional decline and results in poor quality of life and other negative outcomes in older adults. Previous studies have suggested that MCI may represent a condition that predates Alzheimer's disease (AD), based on the high conversion rate for it. With that in mind, the principal aim of this study was to evaluate whether the platelet and plasma levels of ADAM10 could act as biomarkers of the concomitant conditions of MCI and physical frailty, in order to support the new construct of cognitive frailty. The study was carried out with a population aged over 60 years old who were in the coverage of a family health center in the city of São Carlos-SP, Brazil. The subjects were properly assessed for cognition and physical frailty. Subsequently, biological samples were collected, analyzed and stored in a biorepository. The levels of platelet and plasma ADAM10 were analyzed using the Western blot technique in subjects with MCI, compared to subjects without the presence of cognitive impairments, both with and without the presence of frailty. The results indicate that ADAM10 levels are reduced in platelets and increased in plasma of older adults with MCI when compared to healthy controls, regardless of the condition of physical frailty. Based on the results obtained, this study raised the hypothesis that the plasma and soluble form of ADAM10 would be inactive, whereas the platelet form, anchored to the cell plasma membrane, would be active. Thus, we also aimed to assess whether the enzymatic activity of ADAM10 is dependent on its anchoring to the plasma membrane through the evaluation of the enzymatic activity of ADAM10 after the isolation of different fractions of SH-SY5Y neuroblastoma cells. Due to the worldwide pandemic scenario, the enzyme activity assay in cell fractions could not be completed, however a previous study carried out by this research group proved that ADAM10 found in plasma is enzymatically inactive, whereas the platelet form of the protein, was shown to be active, confirming our hypothesis that the reduced levels of active ADAM10 (60 kDa) are related to the condition of MCI, as well as the increased levels of inactive ADAM10 (50 kDa). Taken together, the results demonstrate that ADAM10 cannot be considered as a biomarker in conditions of cognitive frailty, but can act effectively as a low-cost, easy-access and low-invasive biomarker molecule for MCI. These results contribute to a better understanding of the biology of the molecule, as well as for the implantation of tools that promote the diagnosis of MCI. Furthermore, the evidence may guide the health teams to a more adequate planning, with the purpose of improving the quality of life of the older adults affected by this condition, and to direct therapeutic strategies and the prevention of injuries.O Transtorno Neurocognitivo Leve (TNCL), na ausência de demência, e associado à fragilidade física deu origem ao novo conceito de fragilidade cognitiva. Tal definição tem sido considerada como um subtipo de fragilidade que, juntamente com o processo de envelhecimento e sua interação com a fragilidade física, aceleram o ciclo de declínio funcional e resulta em má qualidade de vida e outros desfechos negativos em idosos. Além disso, estudos prévios têm sugerido que o TNCL pode representar uma condição que antecede a doença de Alzheimer (DA), tendo em vista a alta taxa de conversão para a mesma. Com base nisto, este estudo teve como objetivo geral avaliar se os níveis plaquetários e plasmáticos de ADAM10 poderiam atuar como biomarcadores das condições concomitantes de TNCL e fragilidade física, de modo a dar suporte ao novo construto de fragilidade cognitiva. O estudo foi realizado com uma população de idade superior ou igual a 60 anos que estavam na cobertura de um núcleo de saúde da família do município de São Carlos - SP, Brasil. Os participantes foram devidamente avaliados quanto aos quesitos cognição e fragilidade física. Posteriormente, amostras biológicas foram coletadas, analisadas e armazenadas em um biorrepositório. Os níveis de ADAM10 plaquetária e plasmática foram analisados através da técnica de Western Blotting em participantes com TNCL, em comparação com participantes sem a presença de alterações cognitivas, ambos com e sem a presença de fragilidade. Os resultados indicam que os níveis da ADAM10 estão reduzidos em plaquetas e aumentados em plasma de idosos com TNCL em comparação com os controles saudáveis, de forma independente da condição de fragilidade física. Dados os resultados obtidos, este estudo levantou a hipótese de que a forma plasmática e solúvel de ADAM10 estaria inativa, ao passo que a forma plaquetária, ancorada à membrana plasmática, estaria ativa. Assim, foi desenhado um novo objetivo para este estudo, que consistiu em avaliar se a atividade enzimática da ADAM10 é dependente de sua ancoragem à membrana plasmática. Para esse fim, durante o estágio no exterior, buscou-se desenvolver um protocolo de isolamento da membrana plasmática por fracionamento de células de neuroblastoma da linhagem SH-SY5Y, e testar a atividade enzimática da ADAM10 nas diferentes frações. Em decorrência do cenário pandêmico mundial o ensaio de atividade enzimática nas frações celulares não pôde ser concluído, contudo um estudo prévio (ainda não publicado), realizado por nosso grupo de pesquisa, comprovou que a ADAM10 encontrada no plasma é enzimaticamente inativa, ao passo que a forma plaquetária da proteína, mostrou-se ativa. Estes resultados demonstram que, de fato, os níveis reduzidos de ADAM10 ativa (60 kDa) estão relacionados a condição de TNCL, assim como o aumento dos níveis de ADAM10 inativa (50 kDa). Tomados em conjunto, os resultados demonstram que a ADAM10 não pode ser considerada como biomarcadora em condições de fragilidade cognitiva, mas que pode atuar de forma eficaz como biomarcadora de baixo custo, fácil acesso e pouco invasiva para o TNCL. Estes resultados devem contribuir para um melhor entendimento da biologia da molécula, bem como para implantação de ferramentas que atuem no diagnóstico de TNCL, de forma a auxiliar no planejamento mais adequado das equipes de saúde, com o objetivo de aprimorar a qualidade de vida dos idosos com esta condição, além de direcionar conduta terapêutica e prevenir agravos.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)FAPESP: 2016/06226-9porUniversidade Federal de São CarlosCâmpus São CarlosPrograma Interinstitucional de Pós-Graduação em Ciências Fisiológicas - PIPGCFUFSCarAttribution-NonCommercial-NoDerivs 3.0 Brazilhttp://creativecommons.org/licenses/by-nc-nd/3.0/br/info:eu-repo/semantics/openAccessIdosoEnvelhecimentoTranstorno Neurocognitivo Leve (TNCL)Fragilidade cognitivaBiomarcadoresAtividadeADAM10Older peopleAgingMild Cognitive Impairment (MCI)Cognitive frailtyBiomarkersActivityCIENCIAS BIOLOGICASADAM10 como biomarcadora de Transtorno Neurocognitivo LeveADAM10 as a biomarker for Mild Cognitive Impairmentinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesis6006006fbc146e-b953-4aee-ae8e-f34e0b675891reponame:Repositório Institucional da UFSCARinstname:Universidade Federal de São Carlos (UFSCAR)instacron:UFSCARORIGINALTese de doutorado - Izabela Pereira Vatanabe.pdfTese de doutorado - Izabela Pereira Vatanabe.pdfTese de doutorado - Izabela Pereira Vatanabe.application/pdf6052295https://repositorio.ufscar.br/bitstream/ufscar/13363/5/Tese%20de%20doutorado%20-%20Izabela%20Pereira%20Vatanabe.pdf6254219d9273b8b469500e2f45be81e0MD55Carta - pedido de homologação da Tese - Izabela Pereira Vatanabe.pdfCarta - pedido de homologação da Tese - Izabela Pereira Vatanabe.pdfapplication/pdf224581https://repositorio.ufscar.br/bitstream/ufscar/13363/4/Carta%20-%20pedido%20de%20homologa%c3%a7%c3%a3o%20da%20Tese%20-%20Izabela%20Pereira%20Vatanabe.pdff9a480fd2df30494a059e9e9a4d9b92eMD54CC-LICENSElicense_rdflicense_rdfapplication/rdf+xml; charset=utf-8811https://repositorio.ufscar.br/bitstream/ufscar/13363/6/license_rdfe39d27027a6cc9cb039ad269a5db8e34MD56TEXTTese de doutorado - Izabela Pereira Vatanabe.pdf.txtTese de doutorado - Izabela Pereira Vatanabe.pdf.txtExtracted texttext/plain238323https://repositorio.ufscar.br/bitstream/ufscar/13363/7/Tese%20de%20doutorado%20-%20Izabela%20Pereira%20Vatanabe.pdf.txt862d588fbffd87b30fede3ac6afac9aaMD57Carta - pedido de homologação da Tese - Izabela Pereira Vatanabe.pdf.txtCarta - pedido de homologação da Tese - Izabela Pereira Vatanabe.pdf.txtExtracted texttext/plain1837https://repositorio.ufscar.br/bitstream/ufscar/13363/9/Carta%20-%20pedido%20de%20homologa%c3%a7%c3%a3o%20da%20Tese%20-%20Izabela%20Pereira%20Vatanabe.pdf.txt90de3d7d3d2dbed25d6f7255ce187b95MD59THUMBNAILTese de doutorado - Izabela Pereira Vatanabe.pdf.jpgTese de doutorado - Izabela Pereira Vatanabe.pdf.jpgIM Thumbnailimage/jpeg7229https://repositorio.ufscar.br/bitstream/ufscar/13363/8/Tese%20de%20doutorado%20-%20Izabela%20Pereira%20Vatanabe.pdf.jpg2d6306791fea169e920504a879bd9806MD58Carta - pedido de homologação da Tese - Izabela Pereira Vatanabe.pdf.jpgCarta - pedido de homologação da Tese - Izabela Pereira Vatanabe.pdf.jpgIM Thumbnailimage/jpeg5649https://repositorio.ufscar.br/bitstream/ufscar/13363/10/Carta%20-%20pedido%20de%20homologa%c3%a7%c3%a3o%20da%20Tese%20-%20Izabela%20Pereira%20Vatanabe.pdf.jpg3e327981f8699d5e10962a0ac149681aMD510ufscar/133632023-09-18 18:32:03.205oai:repositorio.ufscar.br:ufscar/13363Repositório InstitucionalPUBhttps://repositorio.ufscar.br/oai/requestopendoar:43222023-09-18T18:32:03Repositório Institucional da UFSCAR - Universidade Federal de São Carlos (UFSCAR)false
dc.title.por.fl_str_mv ADAM10 como biomarcadora de Transtorno Neurocognitivo Leve
dc.title.alternative.eng.fl_str_mv ADAM10 as a biomarker for Mild Cognitive Impairment
title ADAM10 como biomarcadora de Transtorno Neurocognitivo Leve
spellingShingle ADAM10 como biomarcadora de Transtorno Neurocognitivo Leve
Vatanabe, Izabela Pereira
Idoso
Envelhecimento
Transtorno Neurocognitivo Leve (TNCL)
Fragilidade cognitiva
Biomarcadores
Atividade
ADAM10
Older people
Aging
Mild Cognitive Impairment (MCI)
Cognitive frailty
Biomarkers
Activity
CIENCIAS BIOLOGICAS
title_short ADAM10 como biomarcadora de Transtorno Neurocognitivo Leve
title_full ADAM10 como biomarcadora de Transtorno Neurocognitivo Leve
title_fullStr ADAM10 como biomarcadora de Transtorno Neurocognitivo Leve
title_full_unstemmed ADAM10 como biomarcadora de Transtorno Neurocognitivo Leve
title_sort ADAM10 como biomarcadora de Transtorno Neurocognitivo Leve
author Vatanabe, Izabela Pereira
author_facet Vatanabe, Izabela Pereira
author_role author
dc.contributor.authorlattes.por.fl_str_mv http://lattes.cnpq.br/3546552931158643
dc.contributor.author.fl_str_mv Vatanabe, Izabela Pereira
dc.contributor.advisor1.fl_str_mv Cominetti, Márcia Regina
dc.contributor.advisor1Lattes.fl_str_mv http://lattes.cnpq.br/3725318894555272
dc.contributor.advisor-co1.fl_str_mv Manzine, Patricia Regina
dc.contributor.advisor-co1Lattes.fl_str_mv http://lattes.cnpq.br/6348503930553992
dc.contributor.authorID.fl_str_mv 9eb5cd72-a42c-4864-bdb8-cd40bb4c5751
contributor_str_mv Cominetti, Márcia Regina
Manzine, Patricia Regina
dc.subject.por.fl_str_mv Idoso
Envelhecimento
Transtorno Neurocognitivo Leve (TNCL)
Fragilidade cognitiva
Biomarcadores
Atividade
ADAM10
topic Idoso
Envelhecimento
Transtorno Neurocognitivo Leve (TNCL)
Fragilidade cognitiva
Biomarcadores
Atividade
ADAM10
Older people
Aging
Mild Cognitive Impairment (MCI)
Cognitive frailty
Biomarkers
Activity
CIENCIAS BIOLOGICAS
dc.subject.eng.fl_str_mv Older people
Aging
Mild Cognitive Impairment (MCI)
Cognitive frailty
Biomarkers
Activity
dc.subject.cnpq.fl_str_mv CIENCIAS BIOLOGICAS
description Mild cognitive impairment (MCI), in the absence of dementia, and associated with physical frailty gave rise to the new concept called cognitive frailty. This new concept has also been considered as a subtype of frailty. Moreover, along with the aging process and its interaction with physical frailty, it accelerates the cycle of functional decline and results in poor quality of life and other negative outcomes in older adults. Previous studies have suggested that MCI may represent a condition that predates Alzheimer's disease (AD), based on the high conversion rate for it. With that in mind, the principal aim of this study was to evaluate whether the platelet and plasma levels of ADAM10 could act as biomarkers of the concomitant conditions of MCI and physical frailty, in order to support the new construct of cognitive frailty. The study was carried out with a population aged over 60 years old who were in the coverage of a family health center in the city of São Carlos-SP, Brazil. The subjects were properly assessed for cognition and physical frailty. Subsequently, biological samples were collected, analyzed and stored in a biorepository. The levels of platelet and plasma ADAM10 were analyzed using the Western blot technique in subjects with MCI, compared to subjects without the presence of cognitive impairments, both with and without the presence of frailty. The results indicate that ADAM10 levels are reduced in platelets and increased in plasma of older adults with MCI when compared to healthy controls, regardless of the condition of physical frailty. Based on the results obtained, this study raised the hypothesis that the plasma and soluble form of ADAM10 would be inactive, whereas the platelet form, anchored to the cell plasma membrane, would be active. Thus, we also aimed to assess whether the enzymatic activity of ADAM10 is dependent on its anchoring to the plasma membrane through the evaluation of the enzymatic activity of ADAM10 after the isolation of different fractions of SH-SY5Y neuroblastoma cells. Due to the worldwide pandemic scenario, the enzyme activity assay in cell fractions could not be completed, however a previous study carried out by this research group proved that ADAM10 found in plasma is enzymatically inactive, whereas the platelet form of the protein, was shown to be active, confirming our hypothesis that the reduced levels of active ADAM10 (60 kDa) are related to the condition of MCI, as well as the increased levels of inactive ADAM10 (50 kDa). Taken together, the results demonstrate that ADAM10 cannot be considered as a biomarker in conditions of cognitive frailty, but can act effectively as a low-cost, easy-access and low-invasive biomarker molecule for MCI. These results contribute to a better understanding of the biology of the molecule, as well as for the implantation of tools that promote the diagnosis of MCI. Furthermore, the evidence may guide the health teams to a more adequate planning, with the purpose of improving the quality of life of the older adults affected by this condition, and to direct therapeutic strategies and the prevention of injuries.
publishDate 2020
dc.date.accessioned.fl_str_mv 2020-10-22T17:37:04Z
dc.date.available.fl_str_mv 2020-10-22T17:37:04Z
dc.date.issued.fl_str_mv 2020-09-28
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dc.identifier.citation.fl_str_mv VATANABE, Izabela Pereira. ADAM10 como biomarcadora de Transtorno Neurocognitivo Leve. 2020. Tese (Doutorado em Ciências Fisiológicas) – Universidade Federal de São Carlos, São Carlos, 2020. Disponível em: https://repositorio.ufscar.br/handle/ufscar/13363.
dc.identifier.uri.fl_str_mv https://repositorio.ufscar.br/handle/ufscar/13363
identifier_str_mv VATANABE, Izabela Pereira. ADAM10 como biomarcadora de Transtorno Neurocognitivo Leve. 2020. Tese (Doutorado em Ciências Fisiológicas) – Universidade Federal de São Carlos, São Carlos, 2020. Disponível em: https://repositorio.ufscar.br/handle/ufscar/13363.
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