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REVIEW article
Front. Neurosci.
Sec. Neurodegeneration
Volume 19 - 2025 | doi: 10.3389/fnins.2025.1553064
This article is part of the Research Topic Molecular mechanisms of neurodegeneration View all 4 articles
The role of intracellular and extracellular copper compartmentalization in Alzheimer's disease (AD) pathology and its implications for diagnostic and therapeutic
Provisionally accepted- 1 School of Public Health, Gansu University of Chinese Medicine, Lanzhou, Gansu Province, China
- 2 Air Force Medical University, Xi'an, China
Copper is an indispensable trace element for cellular physiology, integral to cellular redox balance and a constituent of enzyme active sites, thereby playing a pivotal role in cellular physiological function. Concerning the pathogenesis of Alzheimer's disease (AD), the homeostatic balance of copper is perturbed both intracellularly and extracellularly. The copper-amyloid precursor protein (APP) complex facilitates the efflux of copper from cells, leading to intracellular copper depletion. Concurrently, extracellular copper associates with amyloid-beta (Aβ) plaques, precipitating copper-enriched Aβ deposition, and augmenting reactive oxygen species (ROS) in brain tissue, culminating in oxidative brain damage. The interaction between copper and APP enhances the α-secretase pathway of APP processing while suppressing the β-secretase pathway, resulting in an increased production of soluble APP (sAPP), which contributes to neuroinflammation in brain tissue. Utilizing the affinity of copper for Aβ plaques, the application of chelating agents to sequester copper within the brain can mitigate neurodegeneration associated with AD pathology. Furthermore, the use of metal imaging techniques to detect copper in the brain offers a potential diagnostic tool for the early identification of AD.
Keywords: Alzheimer's disease (AD), copper homeostasis, Oxidative Stress, amyloid precursor protein (APP), diagnosis
Received: 30 Dec 2024; Accepted: 24 Feb 2025.
Copyright: © 2025 Li, Tan, Wu, Zhang, Wang and Zheng. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Tao Wang, Air Force Medical University, Xi'an, China
Gang Zheng, Air Force Medical University, Xi'an, China
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