Impacts of Iron Metabolism Dysregulation on Alzheimer's Disease.
J Alzheimers Dis
; 80(4): 1439-1450, 2021.
Article
en En
| MEDLINE
| ID: mdl-33682709
ABSTRACT
BACKGROUND:
Iron plays an important role in maintaining cell survival, with normal iron trafficking known to be regulated by the ceruloplasmin-transferrin (Cp-Tf) antioxidant system. Disruption to this system is thought to be detrimental to normal brain function.OBJECTIVE:
To determine whether an imbalance of iron and the proteins involved in its metabolism (ceruloplasmin and transferrin) are linked to Alzheimer's disease (AD) and to the expression of amyloid-beta (Aß) peptide 1-42 (Aß1-42), which is a major species of Aß, and the most toxic.METHODS:
We evaluated the concentrations of iron, calcium, magnesium, and Aß1-42 in the cerebrospinal fluid (CSF) of patients with AD and cognitively normal controls. Correlations between the components of the Cp-Tf antioxidant system in plasma were studied to determine the role of peripheral blood in the onset and/or development of AD. We used commercial ELISA immunoassays to measure Aß1-42, immunoturbidimetry to quantify ceruloplasmin and transferrin, and colorimetry to quantify iron, calcium, and magnesium.RESULTS:
We found that the AD group had lower CSF concentrations of Aß1-42 (pâ<â0.001) and calcium (pâ<â0.001), but a higher CSF concentration of iron (pâ<â0.001). Significantly lower plasma concentrations of ceruloplasmin (pâ=â0.003), transferrin (mean, pâ<â0.001), and iron (pâ<â0.001) were observed in the AD group than in cognitively normal adults. Moreover, we found a strong interdependence between most of these components.CONCLUSION:
Iron dyshomeostasis has a crucial role in the onset of AD and/or its development. Correcting metal misdistribution is an appealing therapeutic strategy for AD.Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Ceruloplasmina
/
Transferrina
/
Enfermedad de Alzheimer
/
Hierro
Tipo de estudio:
Diagnostic_studies
/
Observational_studies
Límite:
Aged
/
Female
/
Humans
/
Male
/
Middle aged
Idioma:
En
Revista:
J Alzheimers Dis
Asunto de la revista:
GERIATRIA
/
NEUROLOGIA
Año:
2021
Tipo del documento:
Article
País de afiliación:
Túnez