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Their alterations in AD, identified prior to amyloid plaque aggregation, offer a unique target for staging pre-amyloid AD. However, analysing their levels in the brain is extremely challenging, necessitating the development of alternative approaches. Here, we utilized laser ablation\u2013inductively coupled plasma\u2013mass spectrometry and solution nebulization\u2013inductively coupled plasma\u2013mass spectrometry to quantitatively measure Cu, Fe, and Zn concentrations in the retina and hippocampus samples obtained from human donors (i.e. AD and healthy controls), and in the amyloid precursor protein\/presenilin 1 (APP\/PS1) mouse model of AD and wild-type (WT) controls, aged 9 and 18 months. Our findings revealed significantly elevated Cu, Fe, and Zn levels in the retina (*P\u00a0&amp;lt;\u00a0.05, P\u00a0&amp;lt;\u00a0.01, and P\u00a0&amp;lt;\u00a0.001) and hippocampus (*P\u00a0&amp;lt;\u00a0.05, *P\u00a0&amp;lt;\u00a0.05, and *P\u00a0&amp;lt;\u00a0.05) of human AD samples compared to healthy controls. Conversely, APP\/PS1 mouse models exhibited notably lower metal levels in the same regions compared to WT mice\u2014Cu, Fe, and Zn levels in the retina (**P\u00a0&amp;lt;\u00a0.01, *P\u00a0&amp;lt;\u00a0.05, and *P\u00a0&amp;lt;\u00a0.05) and hippocampus (**P\u00a0&amp;lt;\u00a0.01, **P\u00a0&amp;lt;\u00a0.01, and *P\u00a0&amp;lt;\u00a0.05). The contrasting metal profiles in human and mouse samples, yet similar patterns within each species\u2019 retina and brain, suggest the retina mirrors cerebral metal dyshomoeostasis in AD. Our findings lay the groundwork for staging pre-AD pathophysiology through assessment of transition metal levels in the retina.<\/jats:p>","DOI":"10.1093\/mtomcs\/mfae053","type":"journal-article","created":{"date-parts":[[2024,11,6]],"date-time":"2024-11-06T23:26:29Z","timestamp":1730935589000},"source":"Crossref","is-referenced-by-count":13,"title":["Alterations in zinc, copper, and iron levels in the retina and brain of Alzheimer's disease patients and the APP\/PS1 mouse model"],"prefix":"10.1093","volume":"16","author":[{"given":"Seyed Mostafa","family":"Hosseinpour Mashkani","sequence":"first","affiliation":[{"name":"Institute for Biomedical Materials and Devices, School of Mathematical and Physical Sciences, Faculty of Science, University of Technology Sydney, Sydney, NSW 2007 ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David P","family":"Bishop","sequence":"additional","affiliation":[{"name":"Hyphenated Mass Spectrometry Laboratory, School of Mathematical and Physical Sciences, University of Technology Sydney , Broadway, Sydney, NSW 2007 ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mika T","family":"Westerhausen","sequence":"additional","affiliation":[{"name":"Hyphenated Mass Spectrometry Laboratory, School of Mathematical and Physical Sciences, University of Technology Sydney , Broadway, Sydney, NSW 2007 ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul A","family":"Adlard","sequence":"additional","affiliation":[{"name":"Synaptic Neurobiology Laboratory, The Florey Institute of Neuroscience and Mental Health, The University of Melbourne , Melbourne 3010 ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S Mojtaba","family":"Golzan","sequence":"additional","affiliation":[{"name":"Vision Science Group (Orthoptics Discipline), Graduate School of Health, University of Technology Sydney , 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