About This Project

Alzheimer's Disease, the 6th leading cause of US deaths, is characterized by amyloid-beta(Aβ) plaques and trace metal level imbalances. How this interaction occurs on the molecular level is currently unknown. Protein HSP-16.2 is known to interact individually with Cu,Zn,and Aβ, but their combined interaction has not yet been researched. I hypothesize that HSP-16.2 is involved in the binding of Aβ to Cu and Zn and increases in the levels of one trace metal cause increases in Aβ and other metals.

Ask the Scientists

What is the context of this research?

Trace metal level imbalances are known to naturally occur in a majority of the aging population, especially in Alzheimer's Disease (AD) patients. Aβ plaques, which characterize AD, are known to bind to Cu and Zn with high affinity. Current research does not address the molecular pathways that characterize this Cu-Zn-Aβ interaction and whether an increase in one trace metal directly causes an increase in other trace metals and Aβ. This research plans to address these knowledge gaps by using C. elegans, a transparent nematode whose neural pathways have been fully established, as a model. HSP-16.2 is a protein known to interact with Cu, Zn, and Aβ individually. By examining its role in the combined Cu-Zn-Aβ interaction, a Cu-Zn-Aβ interaction pathway will potentially be suggested.

What is the significance of this project?

Alzheimer’s Disease is the 6th leading cause of US death, with 1 in 10 people age 65 or older having AD! Since there is currently no cure, better understanding AD pathogenesis is crucial as the size of the elderly population continues to grow. Most publications that explore the relationship between trace metals and Aβ have found that increases in Cu and Zn individually cause increases in Aβ. There are, however, some contradictory reports. The molecular mechanisms driving this causal relationship are not well understood. Finally, whether an increase in one trace metal is the cause of increases in other trace metals in addition to Aβ has not been well explored. Better understanding how Cu, Zn, and Aβ interact will help develop a cure that targets the correct molecular pathways.

What are the goals of the project?

The research goal is to test the relationship of Cu and Zn on Aβ and how they interact.

Phase 1: C. elegans, a model for Alzheimer's Disease, will be supplemented with trace metals Cu and Zn individually to demonstrate whether an increase in one trace metal causes an increase in other trace metals and Aβ aggregation development. Aβ will be measured using Congo Red dye and Cu and Zn will be measured using assays.

Phase 2: The expression level of protein HSP-16.2, which is known to individually interact with Cu, Zn, and Aβ, will be measured over the lifespan of an amyloid-beta producing C. elegans strain that mimics AD progression to suggest potential molecular interaction pathways through which Cu, Zn, and Aβ interact. HSP-16.2 expression will be measured via fluorescent illumination.