Summary: “Zinc-Aβ interaction and its toxicity on brain cells” Zinc is essential for health and is the second abundant trace element in human brain. Zinc dyshomeostasis is implicated in the elderly population and Alzheimer’s disease (AD) which has many other risk factors besides Aβ and tau. Emerging evidence demonstrated that zinc also plays an important role in the pathogenesis of AD such as Aβ production and aggregation, tau phosphorylation, redox homeostasis, and brain-derived neurotrophic factor (BDNF) signaling. Zinc dyshomeostasis could be a therapeutic target for AD treatment. However, there are still controversies on the zinc concentration alteration, and the effect of zinc overload or zinc deficiency in AD patients, mouse models and cell lines. Providing these significant discrepancies across reported studies, more carefully-designed cellular, preclinical and clinical investigations are needed to portray a clearer picture of zinc’s role in AD development before clinical applications. Toward this end, we aim to investigate the interactions between zinc and Aβ, effect of zinc binding on Aβ aggregation, and the potential toxicity of Zn-chelated Aβ (ZnAβ) species on a variety of brain cells including neurons, microglia, astrocytes, and cerebrovascular cells in this one- year supplemental project.