A copper-lowering strategy attenuates amyloid pathology in a transgenic mouse model of Alzheimer's disease.
There is increasing evidence for the crucial role of metals in the pathology of Alzheimer's disease. Both the aggregation and neurotoxicity of amyloid-β are dependent on the presence of copper. This study investigated the ability of the copper-complexing drug tetrathiomolybdate to reduce amyloid-β pathology and spatial memory impairment in both a prevention and a treatment paradigm in the Tg2576 mouse model of Alzheimer's disease. Tetrathiomolybdate treatment lowered brain copper and reduced amyloid-β levels in the prevention paradigm, but not in the treatment paradigm. Our data suggests that controlled lowering of systemic copper may achieve anti-amyloid effects if initiated early in the disease process.
Quinn
Joseph F
JF
Portland Veterans Affairs Medical Center, P3 R&D, Portland, OR, USA. quinnj@ohsu.edu
Harris
Christopher J
CJ
Cobb
Katherine E
KE
Domes
Christopher
C
Ralle
Martina
M
Brewer
George
G
Wadsworth
Teri L
TL
D000544:Alzheimer Disease / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000704:Analysis of Variance; D000818:Animals; D015153:Blotting, Western; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D002570:Ceruloplasmin / Q000378:metabolism; D002614:Chelating Agents / Q000627:therapeutic use; D003300:Copper / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D007150:Immunohistochemistry; D018782:Maze Learning / Q000187:drug effects; D008569:Memory Disorders / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D008982:Molybdenum / Q000627:therapeutic use*; D011897:Random Allocation
D016229:Amyloid beta-Peptides; D002614:Chelating Agents; D003300:Copper; D008982:Molybdenum; C020809:tetrathiomolybdate; D002570:Ceruloplasmin