{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T16:30:52Z","timestamp":1792859452957,"version":"4.5.0"},"reference-count":68,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2021,2,21]],"date-time":"2021-02-21T00:00:00Z","timestamp":1613865600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001321","name":"National Research Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001321","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Anatomy"],"published-print":{"date-parts":[[2021,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Dyshomeostasis of trace elements have been implicated in the progression of Alzheimer's disease (AD), which is characterized by amyloid\u2010\u03b2 (A\u03b2) plaques. Trace elements are particularly associated with the A\u03b2 plaques. Metal\u2010protein attenuating compounds have been developed to inhibit metals from binding to A\u03b2 proteins, which result in A\u03b2 termination, in the hope of improving cognitive functioning. However, there are still some contradicting reports. This review aims to first establish which trace elements are increased or decreased in the brains of Alzheimer's patients, and secondly, to review the effectiveness of clinical trials with metal\u2010protein attenuating compounds for AD. Studies have consistently reported unchanged or increased iron, contradicting reports for zinc, decreased copper, unchanged or decreased manganese, inconsistent results for calcium, and magnesium seems to be unaffected. However, varied results have been reported for all trace elements. Clinical trials using metal\u2010protein attenuating compounds to treat AD have also reported varied results. Copper chelators have repeatedly been used in clinical trials, even though few studies report increased brain copper levels in AD patients. Homeostasis of copper levels is important since copper has a vital role in several enzymes, such as cytochrome c, Cu\/Zn superoxide dismutase and ceruloplasmin. Dyshomeostasis of copper levels can lead to increased oxidative stress and neuronal loss. Future studies should assess a variety of trace element levels in moderately and severely affected AD patients since there are contradicting reports. This review thus provides some insight into trace element alterations in the brains of individuals with AD.<\/jats:p>","DOI":"10.1002\/ca.23727","type":"journal-article","created":{"date-parts":[[2021,2,13]],"date-time":"2021-02-13T14:57:28Z","timestamp":1613228248000},"page":"766-773","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Trace element alterations in Alzheimer's disease: A review"],"prefix":"10.1002","volume":"34","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7309-3277","authenticated-orcid":false,"given":"Karen","family":"Cilliers","sequence":"first","affiliation":[{"name":"Department of Biomedical Sciences, Faculty of Medicine and Health Sciences Stellenbosch University  Cape Town Western Cape South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,2,21]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-2000-2103"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/0167-4943(95)00643-Y"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M412034200"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-3223(94)90047-7"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1021\/ac040184q"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1039\/c0mt00074d"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtemb.2011.08.144"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-2008-15208"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11060-015-2022-8"},{"issue":"3","key":"e_1_2_6_11_1","first-page":"339","article-title":"Imbalances of trace elements related to oxidative damage in Alzheimer's disease brain","volume":"19","author":"Cornett C. 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