title: Decrease in APP and CP mRNA expression supports impairment of iron export in Alzheimer's disease patients.
abstract: Alzheimer's disease (AD) is a neurodegenerative disorder of still unknown etiology and the leading cause of dementia worldwide. Besides its main neuropathological hallmarks, a dysfunctional homeostasis of transition metals has been reported to play a pivotal role in the pathogenesis of this disease. Dysregulation of iron (Fe) metabolism in AD has been suggested, particularly at the level of cellular iron efflux. Herein, we intended to further clarify the molecular mechanisms underlying Fe homeostasis in AD. In order to achieve this goal, the expression of specific Fe metabolism-related genes directly involved in Fe regulation and export was assessed in peripheral blood mononuclear cells (PBMCs) from 73AD patients and 74 controls by quantitative PCR. The results obtained showed a significant decrease in the expression of aconitase 1 (ACO1; P=0.007); ceruloplasmin (CP; P<0.001) and amyloid-beta precursor protein (APP; P=0.006) genes in AD patients compared with healthy volunteers. These observations point out to a significant downregulation in the expression of genes associated with ferroportin-mediated cellular Fe export in PBMCs from AD patients, when compared to controls. Taken together, these findings support previous studies suggesting impairment of Fe homeostasis in AD, which may lead to cellular Fe retention and oxidative stress, a typical feature of this disease.
authors.affiliation: Health Promotion and Prevention of Noncommunicable Diseases Department, Instituto Nacional de Saúde Doutor Ricardo Jorge, Lisboa, Portugal.
authors.forename: Cláudia
authors.initials: C
authors.lastname: Guerreiro
authors.affiliation: Human Genetics Department, Instituto Nacional de Saúde Dr. Ricardo Jorge, Lisboa, Portugal.
authors.forename: Bruno
authors.initials: B
authors.lastname: Silva
authors.affiliation: Health Promotion and Prevention of Noncommunicable Diseases Department, Instituto Nacional de Saúde Doutor Ricardo Jorge, Lisboa, Portugal; Instituto Gulbenkian de Ciência, Oeiras, Portugal.
authors.forename: Ângela C
authors.initials: ÂC
authors.lastname: Crespo
authors.affiliation: Health Promotion and Prevention of Noncommunicable Diseases Department, Instituto Nacional de Saúde Doutor Ricardo Jorge, Lisboa, Portugal; University of Lisboa, Faculty of Sciences, BioISI-Biosystems & Integrative Sciences Institute, Campo Grande, Lisboa, Portugal.
authors.forename: Liliana
authors.initials: L
authors.lastname: Marques
authors.affiliation: Neurology Department, Hospital Prof. Dr. Fernando Fonseca, E.P.E., Amadora, Portugal.
authors.forename: Sónia
authors.initials: S
authors.lastname: Costa
authors.affiliation: Neurology Department, Hospital Prof. Dr. Fernando Fonseca, E.P.E., Amadora, Portugal.
authors.forename: Ângela
authors.initials: Â
authors.lastname: Timóteo
authors.affiliation: Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal.
authors.forename: Erica
authors.initials: E
authors.lastname: Marcelino
authors.affiliation: Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal.
authors.forename: Carolina
authors.initials: C
authors.lastname: Maruta
authors.affiliation: Health Promotion and Prevention of Noncommunicable Diseases Department, Instituto Nacional de Saúde Doutor Ricardo Jorge, Lisboa, Portugal.
authors.forename: Arminda
authors.initials: A
authors.lastname: Vilares
authors.affiliation: Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal.
authors.forename: Mafalda
authors.initials: M
authors.lastname: Matos
authors.affiliation: Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal.
authors.forename: Frederico Simões
authors.initials: FS
authors.lastname: Couto
authors.affiliation: Human Genetics Department, Instituto Nacional de Saúde Dr. Ricardo Jorge, Lisboa, Portugal.
authors.forename: Paula
authors.initials: P
authors.lastname: Faustino
authors.affiliation: Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal.
authors.forename: Ana
authors.initials: A
authors.lastname: Verdelho
authors.affiliation: Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal.
authors.forename: Manuela
authors.initials: M
authors.lastname: Guerreiro
authors.affiliation: Neurology Department, Hospital Prof. Dr. Fernando Fonseca, E.P.E., Amadora, Portugal.
authors.forename: Ana
authors.initials: A
authors.lastname: Herrero
authors.affiliation: Neurology Department, Hospital Prof. Dr. Fernando Fonseca, E.P.E., Amadora, Portugal.
authors.forename: Cristina
authors.initials: C
authors.lastname: Costa
authors.affiliation: Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal.
authors.forename: Alexandre
authors.initials: A
authors.lastname: de Mendonça
authors.affiliation: Instituto Gulbenkian de Ciência, Oeiras, Portugal; Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal. Electronic address: mcmartins227@gmail.com.
authors.forename: Madalena
authors.initials: M
authors.lastname: Martins
authors.affiliation: Health Promotion and Prevention of Noncommunicable Diseases Department, Instituto Nacional de Saúde Doutor Ricardo Jorge, Lisboa, Portugal; University of Lisboa, Faculty of Sciences, BioISI-Biosystems & Integrative Sciences Institute, Campo Grande, Lisboa, Portugal. Electronic address: luciana.costa@insa.min-saude.pt.
authors.forename: Luciana
authors.initials: L
authors.lastname: Costa
keywords: Alzheimer's disease; Cellular iron export; Gene expression; Iron homeostasis