{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T19:09:35Z","timestamp":1793387375648,"version":"4.5.0"},"reference-count":85,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,3,12]],"date-time":"2025-03-12T00:00:00Z","timestamp":1741737600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurosci."],"abstract":"<jats:p>Copper is a trace element indispensable 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\u2019s disease (AD), the homeostatic balance of copper is perturbed both intracellularly and extracellularly. The copper\u2013amyloid precursor protein (APP) complex facilitates the efflux of copper from cells, leading to intracellular copper depletion. Concurrently, extracellular copper associates with amyloid-beta (A\u03b2) plaques, precipitating copper-enriched A\u03b2 deposition and augmenting reactive oxygen species (ROS) in the brain tissue, which finally culminates in oxidative brain damage. The interaction between copper and APP enhances the \u03b1-secretase pathway of APP processing while suppressing the \u03b2-secretase pathway, resulting in an increased production of soluble APP (sAPP), which contributes to neuroinflammation in the brain tissue. Utilizing the affinity of copper for A\u03b2 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.<\/jats:p>","DOI":"10.3389\/fnins.2025.1553064","type":"journal-article","created":{"date-parts":[[2025,3,12]],"date-time":"2025-03-12T07:58:57Z","timestamp":1741766337000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":11,"title":["The role of intracellular and extracellular copper compartmentalization in Alzheimer\u2019s disease pathology and its implications for diagnosis and therapy"],"prefix":"10.3389","volume":"19","author":[{"given":"Yu-Qi","family":"Li","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuang-Shuang","family":"Tan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Di","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gang","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,3,12]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"118","DOI":"10.1016\/j.brainres.2009.11.085","article-title":"Clinical utility of copper, ceruloplasmin, and metallothionein plasma determinations in human neurodegenerative patients and their first-degree relatives","volume":"1319","author":"Arnal","year":"2010","journal-title":"Brain Res."},{"key":"ref2","doi-asserted-by":"publisher","first-page":"895483","DOI":"10.3389\/fchem.2022.895483","article-title":"Novel Coumarin-pyridine hybrids as potent multi-target directed ligands aiming at symptoms of Alzheimer\u2019s disease","volume":"10","author":"Babaei","year":"2022","journal-title":"Front. 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