title: In vivo reduction of amyloid-beta by a mutant copper transporter.
abstract: Cu ions have been suggested to enhance the assembly and pathogenic potential of the Alzheimer's disease amyloid-beta (Abeta) peptide. To explore this relationship in vivo, toxic-milk (txJ) mice with a mutant ATPase7b transporter favoring elevated Cu levels were analyzed in combination with the transgenic (Tg) CRND8 amyloid precursor protein mice exhibiting robust Abeta deposition. Unexpectedly, TgCRND8 mice homozygous for the recessive txJ mutation examined at 6 months of age exhibited a reduced number of amyloid plaques and diminished plasma Abeta levels. In addition, homozygosity for txJ increased survival of young TgCRND8 mice and lowered endogenous CNS Abeta at times before detectable increases in Cu in the CNS. These data suggest that the beneficial effect of the txJ mutation on CNS Abeta burden may proceed by a previously undescribed mechanism, likely involving increased clearance of peripheral pools of Abeta peptide.
authors: Center for Research in Neurodegenerative Diseases, University of Toronto, Toronto, ON, Canada M5S 3H2.
authors: Amie L
authors: AL
authors: Phinney
authors: Bettina
authors: B
authors: Drisaldi
authors: Stephen D
authors: SD
authors: Schmidt
authors: Stan
authors: S
authors: Lugowski
authors: Veronica
authors: V
authors: Coronado
authors: Yan
authors: Y
authors: Liang
authors: Patrick
authors: P
authors: Horne
authors: Jing
authors: J
authors: Yang
authors: Joannis
authors: J
authors: Sekoulidis
authors: Janaky
authors: J
authors: Coomaraswamy
authors: M Azhar
authors: MA
authors: Chishti
authors: Diane W
authors: DW
authors: Cox
authors: Paul M
authors: PM
authors: Mathews
authors: Ralph A
authors: RA
authors: Nixon
authors: George A
authors: GA
authors: Carlson
authors: Peter
authors: P
authors: St George-Hyslop
authors: David
authors: D
authors: Westaway
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics* / Q000378:metabolism*; D053829:Amyloid Precursor Protein Secretases; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism; D000818:Animals; D016282:Aspartic Acid Endopeptidases; D001921:Brain / Q000378:metabolism; D027682:Cation Transport Proteins / Q000235:genetics* / Q000378:metabolism*; D003300:Copper / Q000378:metabolism*; D000073840:Copper-Transporting ATPases; D010450:Endopeptidases / Q000378:metabolism; D005260:Female; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D010641:Phenotype; D011499:Protein Processing, Post-Translational
chemical_list: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D027682:Cation Transport Proteins; D003300:Copper; D053829:Amyloid Precursor Protein Secretases; D010450:Endopeptidases; D016282:Aspartic Acid Endopeptidases; C509282:Bace1 protein, mouse; D000251:Adenosine Triphosphatases; D000073840:Copper-Transporting ATPases