ARS | Publication request: Abundant Expression of Zinc Transporters in the Amyloid Plaques of Alzheimer’s Disease Brain

Submitted to: Elsevier
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: March 25, 2008
Publication Date: April 18, 2008
Repository URL: http://www.sciencedirect.com/science?_ob=MImg&_imagekey=B6SYT-4S9NDSX-2-1&_cdi=4843&_user=4421&_pii=S0361923008001597&_origin=search&_coverDate=09%2F05%2F2008&_sk=999229998&view=c&wchp=dGLbVlW-zSkWb&md5=889f055cea3f0e825d066be4290ca963&ie=/sdarticle.pdf
Citation: Zhang, L., Wang, X., Stoltenberg, M., Danscher, G., Huang, L., Wang, Z. 2008. Abundant Expression of Zinc Transporters in the Amyloid Plaques of Alzheimer’s Disease Brain. Elsevier. Brain Research Bulletin 77 (2008) 55-60.

Interpretive Summary: The pathological key features of Alzheimer’s disease (AD) are formation of senile plaques (SP), extracellular deposits of ß-amyloid peptide (Aß, a short protein fragment formed through cleavage of amyloid precursor protein) in the gray matter of the brain, and neurofibrillary tangles, pathological protein aggregates within neurons of the brain. Previous studies have suggested that an extracellular elevation of zinc concentrations can initiate the deposition of Aß 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 autometallography, a method detecting free zinc ions in the cell, and double immunofluorescence, a method to detect zinc trasnporter and Aß proteins simultaneously in the brain tissue. We found that all the ZNTs tested (ZNT1, 3, 4, 5, 6, 7) were extensively present in the Aß-positive plaques in the cortex (the outermost layers of the cerebrum that controls memory, attention, perceptual awareness, thought, language and consciousness) of human AD brains. Levels of free zinc ions were much higher in the plaques than in the surrounding zinc enriched exon terminals. Moreover, we found an abundant expression of ZNT3 and free zinc ions in the amyloid angiopathic vessels (small blood vessels in the brain in which deposits of amyloid protein in the vessel walls). 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.

Technical Abstract: The pathological key features of Alzheimer’s disease (AD) are ß-amyloid peptide (Aß)-containing senile plaques (SP) and neurofibrillary tangles. Previous studies have suggested that an extracellular elevation of zinc concentrations can initiate the deposition of Aß 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 autometallography and double immunofluorescence for the ZNTs and Aß. We found that all the ZNTs tested (ZNT1, 3, 4, 5, 6, 7) were extensively present in the Aß-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 terminals. Moreover, we found an abundant expression of ZNT3 and autometallographic grains in the amyloid angiopathic vessels. 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.