{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,11]],"date-time":"2026-04-11T13:35:15Z","timestamp":1775914515637,"version":"3.50.1"},"reference-count":29,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2022,2,1]],"date-time":"2022-02-01T00:00:00Z","timestamp":1643673600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2022,2,1]],"date-time":"2022-02-01T00:00:00Z","timestamp":1643673600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2022,2,1]],"date-time":"2022-02-01T00:00:00Z","timestamp":1643673600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2022,2,1]],"date-time":"2022-02-01T00:00:00Z","timestamp":1643673600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2022,2,1]],"date-time":"2022-02-01T00:00:00Z","timestamp":1643673600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2022,2,1]],"date-time":"2022-02-01T00:00:00Z","timestamp":1643673600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2022,2,1]],"date-time":"2022-02-01T00:00:00Z","timestamp":1643673600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["The International Journal of Biochemistry &amp; Cell Biology"],"published-print":{"date-parts":[[2022,2]]},"DOI":"10.1016\/j.biocel.2021.106136","type":"journal-article","created":{"date-parts":[[2021,12,11]],"date-time":"2021-12-11T12:15:48Z","timestamp":1639224948000},"page":"106136","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":11,"special_numbering":"C","title":["Trace concentrations, heavy implications: Influences of biometals on major brain pathologies of Alzheimer\u2019s disease"],"prefix":"10.1016","volume":"143","author":[{"given":"Stephen L.P.","family":"Lippi","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Caroline L.C.","family":"Neely","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anthony L.","family":"Amaya","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"78","reference":[{"key":"10.1016\/j.biocel.2021.106136_bib1","doi-asserted-by":"crossref","first-page":"384","DOI":"10.1016\/j.electacta.2017.03.175","article-title":"Electrochemical studies of tau protein-iron interactions--potential implications for Alzheimer\u2019s disease","volume":"236","author":"Ahmadi","year":"2017","journal-title":"Electrochim. Acta"},{"key":"10.1016\/j.biocel.2021.106136_bib2","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.jinorgbio.2019.02.007","article-title":"Interaction of metal ions with tau protein. The case for a metal-mediated tau aggregation","volume":"194","author":"Ahmadi","year":"2019","journal-title":"J. Inorg. Biochem."},{"issue":"6","key":"10.1016\/j.biocel.2021.106136_bib3","doi-asserted-by":"crossref","first-page":"877","DOI":"10.1016\/j.biocel.2011.02.009","article-title":"Aluminum, copper, iron and zinc differentially alter amyloid-A\u03b2(1-42) aggregation and toxicity","volume":"43","author":"Bolognin","year":"2011","journal-title":"Int. J. Biochem. Cell Biol."},{"issue":"6","key":"10.1016\/j.biocel.2021.106136_bib4","doi-asserted-by":"crossref","first-page":"857","DOI":"10.1016\/j.cell.2010.08.014","article-title":"Iron-export ferroxidase activity of \u03b2-amyloid precursor protein is inhibited by zinc in Alzheimer\u2019s disease","volume":"142","author":"Duce","year":"2010","journal-title":"Cell"},{"issue":"3","key":"10.1016\/j.biocel.2021.106136_bib5","doi-asserted-by":"crossref","first-page":"745","DOI":"10.3233\/JAD-143060","article-title":"The APOE gene is differentially methylated in Alzheimer\u2019s disease","volume":"48","author":"Foraker","year":"2015","journal-title":"J. Alzheimer\u2019s Dis."},{"issue":"2","key":"10.1016\/j.biocel.2021.106136_bib6","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1016\/j.neuint.2012.12.005","article-title":"Deferoxamine inhibits iron induced hippocampal tau phosphorylation in the Alzheimer transgenic mouse brain","volume":"62","author":"Guo","year":"2013","journal-title":"Neurochem. Int."},{"issue":"40","key":"10.1016\/j.biocel.2021.106136_bib7","doi-asserted-by":"crossref","first-page":"10526","DOI":"10.1021\/bi800783d","article-title":"The natively unfolded character of tau and its aggregation to Alzheimer-like paired helical filaments","volume":"47","author":"Jeganathan","year":"2008","journal-title":"Biochemistry"},{"key":"10.1016\/j.biocel.2021.106136_bib8","doi-asserted-by":"crossref","first-page":"1550","DOI":"10.1111\/j.1471-4159.2009.05901.x","article-title":"Chronic copper exposure exacerbates both amyloid and tau pathology and selectively dysregulates cdk5 in a mouse model of AD","volume":"108","author":"Kitazawa","year":"2009","journal-title":"J. Neurochem."},{"issue":"6","key":"10.1016\/j.biocel.2021.106136_bib9","doi-asserted-by":"crossref","first-page":"2058","DOI":"10.1039\/C5FO00219B","article-title":"Ginkgo biloba extract (Egb761) attenuates zinc-induced tau phosphorylation at Ser262 by regulating GSK3\u03b2 activity in rat primary cortical neurons","volume":"6","author":"Kwon","year":"2015","journal-title":"Food Funct."},{"issue":"3","key":"10.1016\/j.biocel.2021.106136_bib10","doi-asserted-by":"crossref","first-page":"831","DOI":"10.1016\/j.celrep.2014.06.047","article-title":"Zinc binding directly regulates tau toxicity independent of tau hyperphosphorylation","volume":"8","author":"Huang","year":"2014","journal-title":"Cell Rep."},{"issue":"4","key":"10.1016\/j.biocel.2021.106136_bib11","doi-asserted-by":"crossref","first-page":"1323","DOI":"10.3233\/JAD-2010-1338","article-title":"Trace copper(II) or zinc(II) ions drastically modify the aggregation behavior of amyloid-0beta1-42: an AFM study","volume":"19","author":"Innocenti","year":"2010","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"10.1016\/j.biocel.2021.106136_bib12","doi-asserted-by":"crossref","first-page":"4772","DOI":"10.1038\/s41598-018-23122-x","article-title":"Zinc ion rapidly induces toxic, off-pathway amyloid-\u03b2 oligomers distinct from amyloid-\u03b2 derived diffusible ligands in Alzheimer\u2019s disease","volume":"8","author":"Lee","year":"2018","journal-title":"Sci. Rep."},{"issue":"6","key":"10.1016\/j.biocel.2021.106136_bib13","doi-asserted-by":"crossref","first-page":"4248","DOI":"10.1074\/jbc.M110.158980","article-title":"Iron promotes the toxicity of amyloid \u03b2 peptide by impediment its ordered aggregation","volume":"286","author":"Liu","year":"2011","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.biocel.2021.106136_bib14","doi-asserted-by":"crossref","first-page":"4595","DOI":"10.1021\/bi982437d","article-title":"Differential effects of Apolipoprotein E isoforms on metal-induced aggregation of A\u03b2 using physiological concentrations","volume":"38","author":"Moir","year":"1999","journal-title":"Biochemistry"},{"key":"10.1016\/j.biocel.2021.106136_bib15","doi-asserted-by":"crossref","first-page":"57","DOI":"10.3233\/JAD-2010-1346","article-title":"NMR studies of zinc, copper, and iron binding to histidine, the principal metal ion complexing site of amyloid-\u03b2 peptide","volume":"20","author":"Nair","year":"2010","journal-title":"J. Alzheimer\u2019s Dis."},{"issue":"1","key":"10.1016\/j.biocel.2021.106136_bib16","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1039\/C8MT00203G","article-title":"Cu and Zn interactions with A\u03b2 peptides: consequence of coordination on aggregation and formation of neurotoxic soluble A\u03b2 oligomers","volume":"11","author":"Rana","year":"2019","journal-title":"Metallomics"},{"key":"10.1016\/j.biocel.2021.106136_bib17","doi-asserted-by":"crossref","first-page":"276","DOI":"10.3389\/fnmol.2018.00276","article-title":"Untangling tau and iron: exploring the interaction between iron and tau in neurodegeneration","volume":"11","author":"Rao","year":"2018","journal-title":"Front. Mol. Neurosci."},{"issue":"4","key":"10.1016\/j.biocel.2021.106136_bib18","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1016\/j.jmb.2018.12.008","article-title":"Zinc induces temperature-dependent reversible self-assembly of tau","volume":"431","author":"Roman","year":"2019","journal-title":"J. Mol. Biol."},{"issue":"4","key":"10.1016\/j.biocel.2021.106136_bib19","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1016\/S0891-5849(00)00494-9","article-title":"Redox-active iron mediates amyloid-\u03b2 toxicity","volume":"30","author":"Rottkamp","year":"2001","journal-title":"Free Radic. Biol. Med."},{"issue":"24","key":"10.1016\/j.biocel.2021.106136_bib20","doi-asserted-by":"crossref","first-page":"20522","DOI":"10.1074\/jbc.M111.323279","article-title":"Paired helical filaments from Alzheimer disease brain induce intracellular accumulation of Tau protein in aggresomes","volume":"287","author":"Santa-Maria","year":"2012","journal-title":"J. Biol. Chem."},{"issue":"22","key":"10.1016\/j.biocel.2021.106136_bib21","doi-asserted-by":"crossref","first-page":"15145","DOI":"10.1074\/jbc.M600417200","article-title":"Copper-mediated amyloid-\u03b2 toxicity is associated with an intermolecular histidine bridge","volume":"281","author":"Smith","year":"2006","journal-title":"J. Biol. Chem."},{"issue":"1","key":"10.1016\/j.biocel.2021.106136_bib22","doi-asserted-by":"crossref","first-page":"363","DOI":"10.3233\/JAD-2010-1239","article-title":"Increased iron and free radical generation in preclinical Alzheimer disease and mild cognitive impairment","volume":"19","author":"Smith","year":"2010","journal-title":"J. Alzheimer\u2019s. Dis."},{"issue":"14","key":"10.1016\/j.biocel.2021.106136_bib23","doi-asserted-by":"crossref","first-page":"11174","DOI":"10.1074\/jbc.M111.309070","article-title":"Synaptic released zinc promotes tau hyperphosphorylation by inhibition of protein phosphatase 2A (PP2A)","volume":"287","author":"Sun","year":"2012","journal-title":"J. Biol. Chem."},{"issue":"6","key":"10.1016\/j.biocel.2021.106136_bib24","doi-asserted-by":"crossref","first-page":"1784","DOI":"10.1111\/j.1471-4159.2009.06269.x","article-title":"Zn(II)- and Cu(II)-induced non-fibrillar aggregates of amyloid-beta (1-42) peptide are transformed to amyloid fibrils, both spontaneously and under the influence of metal chelators","volume":"110","author":"T\u00f5ugu","year":"2009","journal-title":"J. Neurochem."},{"key":"10.1016\/j.biocel.2021.106136_bib25","doi-asserted-by":"crossref","first-page":"607","DOI":"10.3389\/fneur.2019.00607","article-title":"Iron deposition leads to hyperphosphorylation of tau and disruption of insulin signaling","volume":"10","author":"Wan","year":"2019","journal-title":"Front. Neurol."},{"issue":"3","key":"10.1016\/j.biocel.2021.106136_bib26","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1007\/s12264-014-1519-z","article-title":"Zinc binds to and directly inhibits protein phosphatase 2A in vitro","volume":"31","author":"Xiong","year":"2015","journal-title":"Neurosci. Bull."},{"issue":"121","key":"10.1016\/j.biocel.2021.106136_bib27","article-title":"Interactions of metals and Apolipoprotein E in Alzheimer\u2019s disease","volume":"6","author":"Xu","year":"2014","journal-title":"Front. Aging Neurosci."},{"key":"10.1016\/j.biocel.2021.106136_bib28","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1016\/j.nbd.2015.06.016","article-title":"Zinc affects the proteolytic stability of Apolipoprotein E in an isoform-dependent way","volume":"81","author":"Xu","year":"2015","journal-title":"Neurobiol. Dis."},{"issue":"2","key":"10.1016\/j.biocel.2021.106136_bib29","doi-asserted-by":"crossref","first-page":"471","DOI":"10.3233\/JAD-150797","article-title":"Iron regulates Apolipoprotein E expression and secretion in neurons and astrocytes","volume":"51","author":"Xu","year":"2016","journal-title":"J. Alzheimer\u2019s Dis."}],"container-title":["The International Journal of Biochemistry &amp; Cell Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S135727252100217X?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S135727252100217X?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,10,23]],"date-time":"2025-10-23T07:21:02Z","timestamp":1761204062000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S135727252100217X"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,2]]},"references-count":29,"alternative-id":["S135727252100217X"],"URL":"https:\/\/doi.org\/10.1016\/j.biocel.2021.106136","relation":{},"ISSN":["1357-2725"],"issn-type":[{"value":"1357-2725","type":"print"}],"subject":[],"published":{"date-parts":[[2022,2]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Trace concentrations, heavy implications: Influences of biometals on major brain pathologies of Alzheimer\u2019s disease","name":"articletitle","label":"Article Title"},{"value":"The International Journal of Biochemistry & Cell Biology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.biocel.2021.106136","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2021 Elsevier Ltd. All rights reserved.","name":"copyright","label":"Copyright"}],"article-number":"106136"}}