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Updated: Jul 26, 2025
Assessing Iron Deposition in the Brains of 5xFAD Mice by Perls'/DAB Staining
Published on: May 23, 2025
Apolipoprotein E is required for brain iron homeostasis in mice
Juan Ma1, Qian Guo2, Meng-Qi Shen3
1Department of Neurology, Affiliated Hospital, and Institute of Translational and Precision Medicine, Nantong University, 19 Qi Xiu Road, Nantong, Jiangsu, 226001, China; Laboratory of Neuropharmacology of Pharmacy School, and National Clinical Research Center for Aging and Medicine of Huashan Hospital, Fudan University, Shanghai, 201203, China.
Background:
Apolipoprotein E deficiency (ApoE-/-) increases progressively iron in the liver, spleen and aortic tissues with age in mice. However, it is unknown whether ApoE affects brain iron.
Methods:
We investigated iron contents, expression of transferrin receptor 1 (TfR1), ferroportin 1 (Fpn1), iron regulatory proteins (IRPs), aconitase, hepcidin, Aβ42, MAP2, reactive oxygen species (ROS), cytokines and glutathione peroxidase 4 (Gpx4) in the brain of ApoE-/- mice.
Results:
We demonstrated that ApoE-/- induced a significant increase in iron, TfR1 and IRPs and a reduction in Fpn1, aconitase and hepcidin in the hippocampus and basal ganglia. We also showed that replenishment of ApoE absent partly reversed the iron-related phenotype in ApoE-/- mice at 24-months old. In addition, ApoE-/- induced a significant increase in Aβ42, MDA, 8-isoprostane, IL-1β, IL-6, and TNFα and a reduction in MAP2 and Gpx4 in hippocampus, basal ganglia and/or cortex of mice at 24-months old.
Conclusions:
Our findings implied that ApoE is required for brain iron homeostasis and ApoE-/--induced increase in brain iron is due to the increased IRP/TfR1-mediated cell-iron uptake as well as the reduced IRP/Fpn1 associated cell-iron export and suggested that ApoE-/- induced neuronal injury resulted mainly from the increased iron and subsequently ROS, inflammation and ferroptosis.
