Abundant expression of zinc transporters in the amyloid plaques of Alzheimer's disease brain

The pathological key features of Alzheimer's disease (AD) are beta-amyloid peptide (A beta)-containing senile plaques (SP) and neurofibrillary tangles. Previous studies have suggested that an extracellular elevation of the zinc concentration can initiate the deposition of A beta and lead to the formation of SP. In the present study, we present data showing a correlation between zinc ions, zinc transporters (ZNTs) and AD, using immersion auto metallography (AMG) and double immunofluorescence for the ZNTs and A beta. We found that all the ZNTs tested (ZNT1, 3,4,5,6, 7) were extensively present in the A beta-positive plaques in the cortex of human AD brains, and the density of autometallographic silver enhanced zinc-sulphur nanoparticles were much higher in the plaques than in the surrounding zinc enriched (ZEN) terminals. Moreover, we found an abundant expression of ZNT3 and autometallographic grains in the amyloid angiopathic vessels. The subcellular localization of ZNTs and zinc ions were not detected, due to the limited tissue preservation in the present study. In conclusion, our data provided significant morphological evidence of zinc ions and ZNTs being actively involved in the pathological processes that lead to plaque formation. (c) 2008 Elsevier Inc. All rights reserved.