Faculty of Sciences of Tunis, University of Tunis El Manar, Tunis, Tunisia.
Faculty of Medicine of Tunis, Neurosciences Department, University of Tunis El Manar, Tunis, Tunisia.
J Alzheimers Dis. 2021;80(4):1439-1450. doi: 10.3233/JAD-201250.
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.
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.
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.
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.
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.
铁在维持细胞存活方面起着重要作用，已知正常的铁转运受铜蓝蛋白-转铁蛋白（Cp-Tf）抗氧化系统的调节。该系统的破坏被认为对正常的大脑功能有害。
确定铁及其代谢相关蛋白（铜蓝蛋白和转铁蛋白）的失衡是否与阿尔茨海默病（AD）以及淀粉样β肽 1-42（Aβ1-42）的表达有关，Aβ1-42 是 Aβ的主要物种，也是最具毒性的。
我们评估了 AD 患者和认知正常对照者脑脊液（CSF）中的铁、钙、镁和 Aβ1-42 浓度。研究了血浆中 Cp-Tf 抗氧化系统成分之间的相关性，以确定外周血在 AD 的发病和/或发展中的作用。我们使用商业 ELISA 免疫测定法测量 Aβ1-42，免疫比浊法定量铜蓝蛋白和转铁蛋白，比色法定量铁、钙和镁。
我们发现 AD 组 CSF 中 Aβ1-42（p<0.001）和钙（p<0.001）浓度较低，但铁（p<0.001）浓度较高。AD 组血浆中铜蓝蛋白（p=0.003）、转铁蛋白（均值，p<0.001）和铁（p<0.001）浓度明显低于认知正常成年人。此外，我们发现这些成分之间存在很强的相互依存关系。
铁动态平衡失调在 AD 的发病和/或发展中起着关键作用。纠正金属分布异常是 AD 的一种有吸引力的治疗策略。
