Dietary Cu stabilizes brain superoxide dismutase 1 activity and reduces amyloid Abeta production in APP23 transgenic mice.
The Cu-binding beta-amyloid precursor protein (APP), and the amyloid Abeta peptide have been proposed to play a role in physiological metal regulation. There is accumulating evidence of an unbalanced Cu homeostasis with a causative or diagnostic link to Alzheimer's disease. Whereas elevated Cu levels are observed in APP knockout mice, APP overexpression results in reduced Cu in transgenic mouse brain. Moreover, Cu induces a decrease in Abeta levels in APP-transfected cells in vitro. To investigate the influence of bioavailable Cu, transgenic APP23 mice received an oral treatment with Cu-supplemented sucrose-sweetened drinking water (1). Chronic APP overexpression per se reduced superoxide dismutase 1 activity in transgenic mouse brain, which could be restored to normal levels after Cu treatment (2). A significant increase of brain Cu indicated its bioavailability on Cu treatment in APP23 mice, whereas Cu levels remained unaffected in littermate controls (3). Cu treatment lowered endogenous CNS Abeta before a detectable reduction of amyloid plaques. Thus, APP23 mice reveal APP-induced alterations linked to Cu homeostasis, which can be reversed by addition of dietary Cu.
Bayer
Thomas A
TA
Department of Psychiatry, Division of Neurobiology, University of the Saarland Medical Center, D-66421 Homburg, Germany. thomas.bayer@uniklinik-saarland.de
Schäfer
Stephanie
S
Simons
Andreas
A
Kemmling
André
A
Kamer
Thomas
T
Tepest
Ralf
R
Eckert
Anne
A
Schüssel
Katrin
K
Eikenberg
Oliver
O
Sturchler-Pierrat
Christine
C
Abramowski
Dorothee
D
Staufenbiel
Matthias
M
Multhaup
Gerd
G
D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000096:biosynthesis*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology; D003300:Copper / Q000378:metabolism / Q000494:pharmacology*; D004032:Diet; D004795:Enzyme Stability / Q000187:drug effects; D005260:Female; D006706:Homeostasis; D007527:Isoenzymes / Q000378:metabolism; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D008959:Models, Neurological; D009154:Mutation; D016874:Neurofibrillary Tangles / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D010641:Phenotype; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism*
D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D007527:Isoenzymes; D011994:Recombinant Proteins; D003300:Copper; D013482:Superoxide Dismutase