Contribution by synaptic zinc to the gender-disparate plaque formation in human Swedish mutant APP transgenic mice

被引:348
作者
Lee, JY
Cole, TB
Palmiter, RD
Suh, SW
Koh, JY [1 ]
机构
[1] Univ Ulsan, Coll Med, Ctr Study Nervous Syst Zinc, Natl Creat Res Initiat Ctr, Seoul 138736, South Korea
[2] Univ Ulsan, Coll Med, Dept Neurol, Seoul 138736, South Korea
[3] Univ Washington, Howard Hughes Med Inst, Dept Biochem, Seattle, WA 98195 USA
[4] Univ Texas, Jennie Sealy Hosp, Med Branch, Dept Anat & Neurosci, Galveston, TX 77555 USA
关键词
D O I
10.1073/pnas.092034699
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Endogenous metals may contribute to the accumulation of amyloid plaques in Alzheimer's disease. To specifically examine the role of synaptic zinc in the plaque accumulation, Tg2576 (also called APP2576) transgenic mice (hAPP(+)) expressing cerebral amyloid plaque pathology were crossed with mice lacking zinc transporter 3 (ZnT3(-/-)), which is required for zinc transport into synaptic vesicles. With aging, female hAPP(+):ZnT3(+/+) mice manifested higher levels of synaptic zinc, insoluble amyloid beta, and plaques than males; these sex differences disappeared in hAPP(+):ZnT3(-/-) mice. Both sexes of hAPP(+):ZnT3(-/-) mice had markedly reduced plaque load and less insoluble amyloid beta compared with hAPP(+):ZnT3(+/+) mice. Hence, of endogenous metals, synaptic zinc contributes predominantly to amyloid deposition in hAPP(+) mice.
引用
收藏
页码:7705 / 7710
页数:6
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