Genetic and biochemical markers in patients with Alzheimer's disease support a concerted systemic iron homeostasis dysregulation

Detalhes bibliográficos
Autor(a) principal: Crespo, A
Data de Publicação: 2014
Outros Autores: Silva, B, Marques, L, Marcelino, E, Maruta, C, Costa, S, Timóteo, A, Vilares, A, Couto, F, Faustino, P, Correia, AP, Verdelho, A, Porto, G, Guerreiro, M, Herrero Valverde, A, Costa, C, Mendonça, A, Costa, L, Martins, M
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10400.10/1515
Resumo: Alzheimer's disease (AD) is the most common form of dementia in the elderly individuals, resulting from a complex interaction between environmental and genetic factors. Impaired brain iron homeostasis has been recognized as an important mechanism underlying the pathogenesis of this disease. Nevertheless, the knowledge gathered so far at the systemic level is clearly insufficient. Herein, we used an integrative approach to study iron metabolism in the periphery, at both genotypic and phenotypic levels, in a sample of 116 patients with AD and 89 healthy control subjects. To assess the potential impact of iron metabolism on the risk of developing AD, genetic analyses were performed along with the evaluation of the iron status profile in peripheral blood by biochemical and gene expression studies. The results obtained showed a significant decrease of serum iron, ferritin, and transferrin concentrations in patients compared with the control subjects. Also, a significant decrease of ferroportin (SLC40A1) and both transferrin receptors TFRC and TFR2 transcripts was found in peripheral blood mononuclear cells from patients. At the genetic level, significant associations with AD were found for single nucleotide polymorphisms in TF, TFR2, ACO1, and SLC40A1 genes. Apolipoprotein E gene, a well-known risk factor for AD, was also found significantly associated with the disease in this study. Taken together, we hypothesize that the alterations on systemic iron status observed in patients could reflect an iron homeostasis dysregulation, particularly in cellular iron efflux. The intracellular iron accumulation would lead to a rise in oxidative damage, contributing to AD pathophysiology.
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spelling Genetic and biochemical markers in patients with Alzheimer's disease support a concerted systemic iron homeostasis dysregulationAlzheimer diseaseAgedHomeostasisBrainIronAlzheimer's disease (AD) is the most common form of dementia in the elderly individuals, resulting from a complex interaction between environmental and genetic factors. Impaired brain iron homeostasis has been recognized as an important mechanism underlying the pathogenesis of this disease. Nevertheless, the knowledge gathered so far at the systemic level is clearly insufficient. Herein, we used an integrative approach to study iron metabolism in the periphery, at both genotypic and phenotypic levels, in a sample of 116 patients with AD and 89 healthy control subjects. To assess the potential impact of iron metabolism on the risk of developing AD, genetic analyses were performed along with the evaluation of the iron status profile in peripheral blood by biochemical and gene expression studies. The results obtained showed a significant decrease of serum iron, ferritin, and transferrin concentrations in patients compared with the control subjects. Also, a significant decrease of ferroportin (SLC40A1) and both transferrin receptors TFRC and TFR2 transcripts was found in peripheral blood mononuclear cells from patients. At the genetic level, significant associations with AD were found for single nucleotide polymorphisms in TF, TFR2, ACO1, and SLC40A1 genes. Apolipoprotein E gene, a well-known risk factor for AD, was also found significantly associated with the disease in this study. Taken together, we hypothesize that the alterations on systemic iron status observed in patients could reflect an iron homeostasis dysregulation, particularly in cellular iron efflux. The intracellular iron accumulation would lead to a rise in oxidative damage, contributing to AD pathophysiology.ElsevierRepositório do Hospital Prof. Doutor Fernando FonsecaCrespo, ASilva, BMarques, LMarcelino, EMaruta, CCosta, STimóteo, AVilares, ACouto, FFaustino, PCorreia, APVerdelho, APorto, GGuerreiro, MHerrero Valverde, ACosta, CMendonça, ACosta, LMartins, M2015-08-24T16:25:00Z2014-01-01T00:00:00Z2014-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10400.10/1515engNeurobiol Aging. 2014 Apr;35(4):777-8510.1016/j.neurobiolaging.2013.10.078metadata only accessinfo: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:RCAAP2022-09-20T15:52:16Zoai:repositorio.hff.min-saude.pt:10400.10/1515Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T15:52:34.123966Repositório 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 Genetic and biochemical markers in patients with Alzheimer's disease support a concerted systemic iron homeostasis dysregulation
title Genetic and biochemical markers in patients with Alzheimer's disease support a concerted systemic iron homeostasis dysregulation
spellingShingle Genetic and biochemical markers in patients with Alzheimer's disease support a concerted systemic iron homeostasis dysregulation
Crespo, A
Alzheimer disease
Aged
Homeostasis
Brain
Iron
title_short Genetic and biochemical markers in patients with Alzheimer's disease support a concerted systemic iron homeostasis dysregulation
title_full Genetic and biochemical markers in patients with Alzheimer's disease support a concerted systemic iron homeostasis dysregulation
title_fullStr Genetic and biochemical markers in patients with Alzheimer's disease support a concerted systemic iron homeostasis dysregulation
title_full_unstemmed Genetic and biochemical markers in patients with Alzheimer's disease support a concerted systemic iron homeostasis dysregulation
title_sort Genetic and biochemical markers in patients with Alzheimer's disease support a concerted systemic iron homeostasis dysregulation
author Crespo, A
author_facet Crespo, A
Silva, B
Marques, L
Marcelino, E
Maruta, C
Costa, S
Timóteo, A
Vilares, A
Couto, F
Faustino, P
Correia, AP
Verdelho, A
Porto, G
Guerreiro, M
Herrero Valverde, A
Costa, C
Mendonça, A
Costa, L
Martins, M
author_role author
author2 Silva, B
Marques, L
Marcelino, E
Maruta, C
Costa, S
Timóteo, A
Vilares, A
Couto, F
Faustino, P
Correia, AP
Verdelho, A
Porto, G
Guerreiro, M
Herrero Valverde, A
Costa, C
Mendonça, A
Costa, L
Martins, M
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Repositório do Hospital Prof. Doutor Fernando Fonseca
dc.contributor.author.fl_str_mv Crespo, A
Silva, B
Marques, L
Marcelino, E
Maruta, C
Costa, S
Timóteo, A
Vilares, A
Couto, F
Faustino, P
Correia, AP
Verdelho, A
Porto, G
Guerreiro, M
Herrero Valverde, A
Costa, C
Mendonça, A
Costa, L
Martins, M
dc.subject.por.fl_str_mv Alzheimer disease
Aged
Homeostasis
Brain
Iron
topic Alzheimer disease
Aged
Homeostasis
Brain
Iron
description Alzheimer's disease (AD) is the most common form of dementia in the elderly individuals, resulting from a complex interaction between environmental and genetic factors. Impaired brain iron homeostasis has been recognized as an important mechanism underlying the pathogenesis of this disease. Nevertheless, the knowledge gathered so far at the systemic level is clearly insufficient. Herein, we used an integrative approach to study iron metabolism in the periphery, at both genotypic and phenotypic levels, in a sample of 116 patients with AD and 89 healthy control subjects. To assess the potential impact of iron metabolism on the risk of developing AD, genetic analyses were performed along with the evaluation of the iron status profile in peripheral blood by biochemical and gene expression studies. The results obtained showed a significant decrease of serum iron, ferritin, and transferrin concentrations in patients compared with the control subjects. Also, a significant decrease of ferroportin (SLC40A1) and both transferrin receptors TFRC and TFR2 transcripts was found in peripheral blood mononuclear cells from patients. At the genetic level, significant associations with AD were found for single nucleotide polymorphisms in TF, TFR2, ACO1, and SLC40A1 genes. Apolipoprotein E gene, a well-known risk factor for AD, was also found significantly associated with the disease in this study. Taken together, we hypothesize that the alterations on systemic iron status observed in patients could reflect an iron homeostasis dysregulation, particularly in cellular iron efflux. The intracellular iron accumulation would lead to a rise in oxidative damage, contributing to AD pathophysiology.
publishDate 2014
dc.date.none.fl_str_mv 2014-01-01T00:00:00Z
2014-01-01T00:00:00Z
2015-08-24T16:25:00Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
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dc.identifier.uri.fl_str_mv http://hdl.handle.net/10400.10/1515
url http://hdl.handle.net/10400.10/1515
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Neurobiol Aging. 2014 Apr;35(4):777-85
10.1016/j.neurobiolaging.2013.10.078
dc.rights.driver.fl_str_mv metadata only access
info:eu-repo/semantics/openAccess
rights_invalid_str_mv metadata only access
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dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
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
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collection Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
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