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Oral zinc reduces amyloid burden in Tg2576 mice.
J Alzheimers Dis. 2014; 41(1):179-92.JA

Abstract

The aggregation of amyloid-β in Alzheimer's disease can be affected by free transition metals such as copper and zinc in the brain. Addition of copper and zinc with amyloid acts to increase aggregation and copper additionally promotes the formation of reactive oxygen species. We propose that reduction of brain copper by blocking uptake of copper from the diet is a viable strategy to regulate the formation of insoluble amyloid-β in the brain of Tg2576 mice. Mice were treated with regimens of zinc acetate, which acts with metallothionein to block copper uptake in the gut, at various times along their lifespan to model prevention and treatment paradigms. We found that the mice tolerated zinc acetate well over the six month course of study. While we did not observe significant changes in cognition and behavior, there was a reduction in insoluble amyloid-β in the brain. This observation coincided with a reduction in brain copper and interestingly no change in brain zinc. Our findings show that blocking copper uptake from the diet can redistribute copper from the brain and reduce amyloid-β aggregation.

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Authors+Show Affiliations

Harris CJ
Department of Neurology, Oregon Health and Sciences University, Portland, OR, USA.
Voss K
Department of Neurology, Oregon Health and Sciences University, Portland, OR, USA.
Murchison C
Department of Neurology, Oregon Health and Sciences University, Portland, OR, USA.
Ralle M
Department of Molecular and Medical Genetics, Oregon Health and Sciences University, Portland, OR, USA.
Frahler K
Department of Neurology, Oregon Health and Sciences University, Portland, OR, USA.
Carter R
Department of Neurology, Oregon Health and Sciences University, Portland, OR, USA.
Rhoads A
Department of Neurology, Oregon Health and Sciences University, Portland, OR, USA.
Lind B
Department of Neurology, Oregon Health and Sciences University, Portland, OR, USA.
Robinson E
Department of Molecular and Medical Genetics, Oregon Health and Sciences University, Portland, OR, USA.
Quinn JF
Department of Neurology and Parkinson's Disease Research Education and Clinical Care Center (PADRECC), Portland Veterans Affairs Medical Center, Portland, OR, USA Department of Neurology, Oregon Health and Sciences University, Portland, OR, USA.

MeSH

Administration, OralAlzheimer DiseaseAmyloid beta-Protein PrecursorAmyloidosisAnimalsBody WeightBrainCeruloplasminCopperDisease Models, AnimalFemaleHumansMaze LearningMice, Inbred C57BLMice, TransgenicMotor ActivityNeuroprotective AgentsRandom AllocationSpatial MemoryZincZinc Acetate

Pub Type(s)

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

Language

eng

PubMed ID

24595193

Citation

Harris, Christopher J., et al. "Oral Zinc Reduces Amyloid Burden in Tg2576 Mice." Journal of Alzheimer's Disease : JAD, vol. 41, no. 1, 2014, pp. 179-92.
Harris CJ, Voss K, Murchison C, et al. Oral zinc reduces amyloid burden in Tg2576 mice. J Alzheimers Dis. 2014;41(1):179-92.
Harris, C. J., Voss, K., Murchison, C., Ralle, M., Frahler, K., Carter, R., Rhoads, A., Lind, B., Robinson, E., & Quinn, J. F. (2014). Oral zinc reduces amyloid burden in Tg2576 mice. Journal of Alzheimer's Disease : JAD, 41(1), 179-92. https://doi.org/10.3233/JAD-131703
Harris CJ, et al. Oral Zinc Reduces Amyloid Burden in Tg2576 Mice. J Alzheimers Dis. 2014;41(1):179-92. PubMed PMID: 24595193.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Oral zinc reduces amyloid burden in Tg2576 mice. AU - Harris,Christopher J, AU - Voss,Kellen, AU - Murchison,Charles, AU - Ralle,Martina, AU - Frahler,Kate, AU - Carter,Raina, AU - Rhoads,Allison, AU - Lind,Betty, AU - Robinson,Emily, AU - Quinn,Joseph F, PY - 2014/3/6/entrez PY - 2014/3/7/pubmed PY - 2015/1/30/medline KW - Alzheimer's disease KW - amyloid-β protein KW - copper KW - transgenic mice SP - 179 EP - 92 JF - Journal of Alzheimer's disease : JAD JO - J Alzheimers Dis VL - 41 IS - 1 N2 - The aggregation of amyloid-β in Alzheimer's disease can be affected by free transition metals such as copper and zinc in the brain. Addition of copper and zinc with amyloid acts to increase aggregation and copper additionally promotes the formation of reactive oxygen species. We propose that reduction of brain copper by blocking uptake of copper from the diet is a viable strategy to regulate the formation of insoluble amyloid-β in the brain of Tg2576 mice. Mice were treated with regimens of zinc acetate, which acts with metallothionein to block copper uptake in the gut, at various times along their lifespan to model prevention and treatment paradigms. We found that the mice tolerated zinc acetate well over the six month course of study. While we did not observe significant changes in cognition and behavior, there was a reduction in insoluble amyloid-β in the brain. This observation coincided with a reduction in brain copper and interestingly no change in brain zinc. Our findings show that blocking copper uptake from the diet can redistribute copper from the brain and reduce amyloid-β aggregation. SN - 1875-8908 UR - https://www.unboundmedicine.com/medline/citation/24595193/full_citation DB - PRIME DP - Unbound Medicine ER -