Expression of iron metabolism: related genes in a portuguese population of Alzheimer’s disease patients
Year: 2013
Type: dissertation
Study design: Observational Study
Abstract: Alzheimer’s disease (AD) is the most common neurodegenerative disorder and one of the most frequent dementia worldwide. The main neuropathological hallmarks of AD are extracellular senile “plaques” (SP) and intracellular neurofibrillary “tangles” (NFT), which are associated with the loss of cortical neurons. This disease is also characterized by elevated brain iron (Fe) levels and accumulation of copper and zinc in cerebral Aβ amyloid deposits, like SP. Thus, a dysfunctional homeostasis of transition metals seems to play pivotal role in pathogenesis of this disease. In this work we intended to further understand the putative role of Fe metabolism in AD pathophysiology. In order to achieve this goal, the expression of specific target Fe metabolism-related genes was measured in peripheral blood mononuclear cells (PBMCs) from AD patients and controls by real time quantitative PCR techniques while Fe status in the periphery was evaluated using biochemical standard techniques. The results obtained showed significant decrease in the expression of acotinase 1 (ACO1; P=0.011); ferroportin (SLC40A1; P<0.001); ceruloplasmin (CP; P<0.001); amyloid peptide precursor (APP; P=0.007); transferrin receptor 1 (TFR1; P<0.001) and transferrin receptor 2 (TFR2; P<0.001) genes, in contrast with an increase in the expression of light chain of ferritin (FT-L; P=0.038) in AD patients compared with healthy volunteers. Also, although we did not find significant differences in Fe metabolism parameters measured in serum, a tendency for the decrease in serum Fe and ferritin (Ft) concentrations was observed in AD patients. These observations reinforce previous reports showing a low Fe status in periphery of AD patients. According to these findings one can suggest impairment in cellular Fe efflux in AD individuals, which may lead to cellular Fe overload and oxidative stress, a typical feature of this disease. Nevertheless, further research into the characterization of regulation of Fe metabolism at both phenotypic and genetic levels in AD may be important to provide a low invasive and earlier form for its diagnosis.
Author: Cláudia C. Guerreiro
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W1536760115