Tags

Type your tag names separated by a space and hit enter

Copper Modulation and Memory Impairment due to Hippocampal Tau Pathology
J Alzheimers Dis. 2020; 78(1):49-60.JA

Abstract

Background:Environmental copper has been implicated in the pathogenesis of Alzheimer’s disease based on evidence that: 1) brain copper levels increase with age, 2) copper promotes misfolding and toxicity of amyloid-β in vitro, 3) copper-modulating interventions reduce amyloid pathology in animal models. However, the effect of copper upon non-amyloid Alzheimer’s 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.

Authors+Show Affiliations

Department of Neurology, Oregon Health and Science University, Portland, OR, USA.Department of Neurology, Oregon Health and Science University, Portland, OR, USA.Department of Neurology, Oregon Health and Science University, Portland, OR, USA.Department of Neurology, Oregon Health and Science University, Portland, OR, USA.Department of Neurology, Oregon Health and Science University, Portland, OR, USA.Department of Neurology, Oregon Health and Science University, Portland, OR, USA. Parkinsons Disease Research, Education, and Clinical Center, Portland Veterans Affairs Medical Center, Portland, OR, USA.

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, Non-P.H.S.

Language

eng

PubMed ID

32250309

Citation

Harris, Christopher J., et al. "Copper Modulation and Memory Impairment Due to Hippocampal Tau Pathology." Journal of Alzheimer's Disease : JAD, vol. 78, no. 1, 2020, pp. 49-60.
Harris CJ, Gray NE, Caruso M, et al. Copper Modulation and Memory Impairment due to Hippocampal Tau Pathology. J Alzheimers Dis. 2020;78(1):49-60.
Harris, C. J., Gray, N. E., Caruso, M., Hunter, M., Ralle, M., & Quinn, J. F. (2020). Copper Modulation and Memory Impairment due to Hippocampal Tau Pathology. Journal of Alzheimer's Disease : JAD, 78(1), 49-60. https://doi.org/10.3233/JAD-200002
Harris CJ, et al. Copper Modulation and Memory Impairment Due to Hippocampal Tau Pathology. J Alzheimers Dis. 2020;78(1):49-60. PubMed PMID: 32250309.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Copper Modulation and Memory Impairment due to Hippocampal Tau Pathology AU - Harris,Christopher J, AU - Gray,Nora E, AU - Caruso,Maya, AU - Hunter,Marguex, AU - Ralle,Martina, AU - Quinn,Joseph F, PY - 2020/4/7/pubmed PY - 2021/9/21/medline PY - 2020/4/7/entrez KW - Coppper KW - neurofibrillary tangles KW - tau KW - zinc SP - 49 EP - 60 JF - Journal of Alzheimer's disease : JAD JO - J Alzheimers Dis VL - 78 IS - 1 N2 - Background:Environmental copper has been implicated in the pathogenesis of Alzheimer’s disease based on evidence that: 1) brain copper levels increase with age, 2) copper promotes misfolding and toxicity of amyloid-β in vitro, 3) copper-modulating interventions reduce amyloid pathology in animal models. However, the effect of copper upon non-amyloid Alzheimer’s 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. SN - 1875-8908 UR - https://www.unboundmedicine.com/medline/citation/32250309/Copper_Modulation_and_Memory_Impairment_due_to_Hippocampal_Tau_Pathology DB - PRIME DP - Unbound Medicine ER -