Altered expression and distribution of zinc transporters in APP/PS1 transgenic mouse brain

Pathological accumulation of beta-amyloid peptide (Abeta) is an early and common feature of Alzheimer's disease (AD). An increased zinc concentration can initiate the deposition of Abeta. The present study aimed to study the expression and distribution patterns of six members of the zinc transporter (ZnT) family, ZnT1, ZnT3, ZnT4, ZnT5, ZnT6, and ZnT7, in the APPswe/PS1dE9 transgenic mouse brain. Our results demonstrated a statistically significant (P<0.05) increase of ZnT1, ZnT3, ZnT4, ZnT6, and ZnT7 in both hippocampus and neo-cortex using Western blot method and an abundant distribution of zinc ions in the plaques and amyloid angiopathic vessels using immersion autometallography. Furthermore, all ZnT immunoreactions were detected in most amyloid plaques and amyloid angiopathic vessels. ZnT1 and ZnT4 were extensively expressed in all parts of the plaques. ZnT3, ZnT5, and ZnT6 were expressed most prominently in the degenerating neurites in the peripheral part of the plaques, while ZnT7 was present in the core of the plaques. The amyloid angiopathic vessels showed a strong ZnT3 immunoreactivity. These results might suggest multiple roles of ZnTs in the deposition and organization of the Abeta composition.