{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T20:47:30Z","timestamp":1783630050571,"version":"3.55.0"},"reference-count":39,"publisher":"SAGE Publications","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAD"],"published-print":{"date-parts":[[2020,10,27]]},"abstract":"<jats:p>Background: Environmental copper has been implicated in the pathogenesis of Alzheimer\u2019s disease based on evidence that: 1) brain copper levels increase with age, 2) copper promotes misfolding and toxicity of amyloid-\u03b2 in vitro, 3) copper-modulating interventions reduce amyloid pathology in animal models. However, the effect of copper upon non-amyloid Alzheimer\u2019s pathology is relatively under-explored. Objective: To determine if modulation of brain copper level affects brain tau pathology and\/or associated cognitive impairment. Methods: We tested the hypothesis that brain copper modulates tau pathology by manipulating brain levels of copper in the PS19 transgenic mouse model of tau pathology. We treated PS19 and wild-type mice with oral zinc acetate, an established therapy for long term control of excess brain copper, and examined treatment effects upon brain copper, brain tau, NFT-like pathology, and spatial memory. We treated a second cohort of mice with exogenous dietary copper in order to evaluate whether excess environmental copper promotes brain tau pathology. Results: Copper-lowering with oral zinc attenuated spatial memory impairment in female but not male PS19 mice, without a significant effect upon tau pathology. Copper loading increased brain copper, but did not have an effect on brain tau pathology or spatial memory function. Conclusion: These findings suggest that a strategy to lower brain copper may be viable for symptomatic benefit in the setting of tau neuropathology, but unlikely to have robust effects on the underlying pathology. These findings are consistent with dietary or other exogenous copper being unlikely to promote tau pathology.<\/jats:p>","DOI":"10.3233\/jad-200002","type":"journal-article","created":{"date-parts":[[2020,4,3]],"date-time":"2020-04-03T10:50:33Z","timestamp":1585911033000},"page":"49-60","source":"Crossref","is-referenced-by-count":11,"title":["Copper Modulation and Memory Impairment due to Hippocampal Tau Pathology"],"prefix":"10.1177","volume":"78","author":[{"given":"Christopher J.","family":"Harris","sequence":"first","affiliation":[{"name":"Department of Neurology, Oregon Health and Science University, Portland, OR, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nora E.","family":"Gray","sequence":"additional","affiliation":[{"name":"Department of Neurology, Oregon Health and Science University, Portland, OR, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maya","family":"Caruso","sequence":"additional","affiliation":[{"name":"Department of Neurology, Oregon Health and Science University, Portland, OR, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marguex","family":"Hunter","sequence":"additional","affiliation":[{"name":"Department of Neurology, Oregon Health and Science University, Portland, OR, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martina","family":"Ralle","sequence":"additional","affiliation":[{"name":"Department of Neurology, Oregon Health and Science University, Portland, OR, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph F.","family":"Quinn","sequence":"additional","affiliation":[{"name":"Department of Neurology, Oregon Health and Science University, Portland, OR, USA"},{"name":"Parkinsons Disease Research, Education, and Clinical Center, Portland Veterans Affairs Medical Center, Portland, OR, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","reference":[{"key":"10.3233\/JAD-200002_ref1","unstructured":"Alzheimer\u2019s Disease Association (2019) Facts and Figures, Alzheimer\u2019s Association National Office: Chicago, IL."},{"key":"10.3233\/JAD-200002_ref2","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1093\/toxsci\/kfy025","article-title":"Environmental and dietary exposure to copper and its cellular mechanisms linking to Alzheimer\u2019s disease","volume":"163","author":"Hsu","year":"2018","journal-title":"Toxicol Sci"},{"key":"10.3233\/JAD-200002_ref3","doi-asserted-by":"crossref","first-page":"1049","DOI":"10.1016\/j.tips.2018.10.001","article-title":"Copper and zinc dysregulation in Alzheimer\u2019s disease","volume":"39","author":"Sensi","year":"2018","journal-title":"Trends Pharmacol 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