Affiliations: [a] Faculty of Sciences of Tunis, University of Tunis El Manar, Tunis, Tunisia
| [b] Faculty of Medicine of Tunis, Neurosciences Department, University of Tunis El Manar, Tunis, Tunisia
| [c]
Biology Laboratory, Children’s Hospital, Tunis, Tunisia
| [d] Neurology Department, National Institute of Neurology, Tunis, Tunisia
| [e] Current address: Institute of Technology, Tralee, Co. Kerry, Ireland
Correspondence:
[*]
Correspondence to: Najla Jouini, Institute of Technology, South Campus Clash Road, Tralee, Co. Kerry, Ireland. E-mail: jouininejla1983@gmail.com.
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 (Aβ) peptide 1–42 (Aβ1–42), which is a major species of Aβ, and the most toxic. Methods:We evaluated the concentrations of iron, calcium, magnesium, and Aβ1–42 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 Aβ1–42, 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 Aβ1–42 (p < 0.001) and calcium (p < 0.001), but a higher CSF concentration of iron (p < 0.001). Significantly lower plasma concentrations of ceruloplasmin (p = 0.003), transferrin (mean, p < 0.001), and iron (p < 0.001) 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.
