For some time, in vitro and human research has indicated that heavy metals such as zinc, copper, or iron, are critical for the aggregation of Aβ into plaques. In vivo evidence now confirms this and traces it specifically to zinc from synaptic vesicles.
In a study published in the April 30 online version of Proceedings of the National Academy of Sciences (USA), Jae-Young Koh's group at the University of Ulsan College of Medicine in Seoul, Korea, along with collaborators in the United States, crossbred mice carrying the Swedish mutant AβPP gene with mice lacking the gene for a protein that transports zinc into synaptic vesicles. As they aged, these mice showed significantly lowered amyloid plaque burdens, suggesting they have high Aβ levels but did not turn it into plaque in the absence of synaptic zinc. Furthermore, the absence of the synaptic zinc pool eliminated previous gender differences whereby female AβPP-transgenic mice had higher plaque burdens than males.
"This result from the Koh group is enormously important," said Chris Frederickson of the University of Texas Medical Branch at Galveston. "When the counter-intuitive approach of trying to block a disease process (plaque deposition) by inducing a genetic defect (the Znt3 knockout) actually works, we all must pay serious attention to the model being tested. Synaptically-released zinc emerges from this work as an undeniable, pivotal part of AD pathogenesis."—Hakon Heimer
No Available References
- Lee JY, Cole TB, Palmiter RD, Suh SW, Koh JY. Contribution by synaptic zinc to the gender-disparate plaque formation in human Swedish mutant APP transgenic mice. Proc Natl Acad Sci U S A. 2002 May 28;99(11):7705-10. PubMed.