期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2003
卷号：100
期号：24
页码：14193-14198
DOI：10.1073/pnas.2332851100
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Cu ions have been suggested to enhance the assembly and pathogenic potential of the Alzheimer's disease amyloid-{beta} (A{beta}) 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 A{beta} 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 A{beta} levels. In addition, homozygosity for txJ increased survival of young TgCRND8 mice and lowered endogenous CNS A{beta} at times before detectable increases in Cu in the CNS. These data suggest that the beneficial effect of the txJ mutation on CNS A{beta} burden may proceed by a previously undescribed mechanism, likely involving increased clearance of peripheral pools of A{beta} peptide.
