Alterations in iron levels in the locus coeruleus of a transgenic Alzheimer’s disease rat model

Abstract

Iron is essential for brain function, acting as a cofactor for enzymes involved in neurotransmitter synthesis and metabolism. However, dysregulated iron homeostasis is increasingly linked to neurodegenerative diseases, including Alzheimer’s disease (AD). The locus coeruleus (LC), a norepinephrine-producing brainstem nucleus, is among the earliest regions affected in AD, yet its iron dynamics remain poorly understood. This study presents the first comprehensive analysis of iron content in the LC by combining a transgenic AD rat model, precise anatomical isolation, and Inductively Coupled Plasma Mass Spectrometry for high-sensitivity metal quantification. This approach enabled the profiling of iron and zinc concentrations in the LC, uncovering novel insights into iron dysregulation in AD. We observed a significant genotype-specific increase in LC iron levels in TgF344-AD rats compared to wild-type controls. Notably, our findings reveal distinct iron alterations in TgF344-AD rats, suggesting a previously unrecognized role for iron homeostasis in LC dysfunction. These results provide new perspectives on iron dysregulation in AD pathology and its potential as a therapeutic target.