title: Oral zinc reduces amyloid burden in Tg2576 mice.
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.
authors.affiliation: Department of Neurology, Oregon Health and Sciences University, Portland, OR, USA.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Harris
authors.affiliation: Department of Neurology, Oregon Health and Sciences University, Portland, OR, USA.
authors.forename: Kellen
authors.initials: K
authors.lastname: Voss
authors.affiliation: Department of Neurology, Oregon Health and Sciences University, Portland, OR, USA.
authors.forename: Charles
authors.initials: C
authors.lastname: Murchison
authors.affiliation: Department of Molecular and Medical Genetics, Oregon Health and Sciences University, Portland, OR, USA.
authors.forename: Martina
authors.initials: M
authors.lastname: Ralle
authors.affiliation: Department of Neurology, Oregon Health and Sciences University, Portland, OR, USA.
authors.forename: Kate
authors.initials: K
authors.lastname: Frahler
authors.affiliation: Department of Neurology, Oregon Health and Sciences University, Portland, OR, USA.
authors.forename: Raina
authors.initials: R
authors.lastname: Carter
authors.affiliation: Department of Neurology, Oregon Health and Sciences University, Portland, OR, USA.
authors.forename: Allison
authors.initials: A
authors.lastname: Rhoads
authors.affiliation: Department of Neurology, Oregon Health and Sciences University, Portland, OR, USA.
authors.forename: Betty
authors.initials: B
authors.lastname: Lind
authors.affiliation: Department of Molecular and Medical Genetics, Oregon Health and Sciences University, Portland, OR, USA.
authors.forename: Emily
authors.initials: E
authors.lastname: Robinson
authors.affiliation: 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.
authors.forename: Joseph F
authors.initials: JF
authors.lastname: Quinn
mesh_terms: D000284:Administration, Oral; D000544:Alzheimer Disease; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000686:Amyloidosis / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology*; D000818:Animals; D001835:Body Weight / Q000187:drug effects / Q000502:physiology; D001921:Brain / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology*; D002570:Ceruloplasmin / Q000378:metabolism; D003300:Copper / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D018696:Neuroprotective Agents / Q000008:administration & dosage*; D011897:Random Allocation; D065852:Spatial Memory / Q000187:drug effects / Q000502:physiology; D015032:Zinc / Q000378:metabolism; D019345:Zinc Acetate / Q000008:administration & dosage*
chemical_list: C545487:APP protein, human; D016564:Amyloid beta-Protein Precursor; D018696:Neuroprotective Agents; D003300:Copper; D002570:Ceruloplasmin; D019345:Zinc Acetate; D015032:Zinc
keywords: Alzheimer's disease; amyloid-β protein; copper; transgenic mice