Contribution by Synaptic Zinc to the Gender-Disparate Plaque Formation in Human Swedish Mutant APP Transgenic Mice

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 l...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2002-05, Vol.99 (11), p.7705-7710
Main Authors: Lee, Joo-Yong, Cole, Toby B., Palmiter, Richard D., Suh, Sang Won, Koh, Jae-Young
Format: Article
Language:English
Subjects:
Aggregation
Aging
Amyloid beta-Protein Precursor - genetics
Amyloids
Animals
Biological Sciences
Brain
Brain - growth & development
Brain - physiology
Female
Fluorescence
Gender differences
Genotypes
Humans
Male
Mice
Mice, Knockout
Mice, Transgenic
Neuroscience
Plaque, Amyloid - genetics
Sex Characteristics
Sweden
Synapses - physiology
Transgenic animals
Zinc
Zinc - physiology
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Summary: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 β, 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 β compared with hAPP+: ZnT3+/+mice. Hence, of endogenous metals, synaptic zinc contributes predominantly to amyloid deposition in hAPP+mice.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.092034699