Multiple lines of evidence show that soluble oligomer forms of amyloid β protein (Aβ42) are the most neurotoxic species in the brain and correlates with the degree of neuronal loss and cognitive deficit in Alzheimer's disease. Although many studies have used mammalian cells to investigate oligomer Aβ42 toxicity, the use of more simple eukaryotic cellular systems offers advantages for large-scale screening studies. We have previously established and validated budding yeast, Saccharomyces cerevisiae to be a simple and a robust model to study the toxicity of Aβ. Using colony counting based methods, oligomeric Aβ42 was shown to induce dose-dependent cell death in yeast. We have adapted this method for high throughput screening by developing an absorbance-based growth assay. We further validated the assay with treatments previously shown to protect oligomer Aβ42 induced cell death in mammalian and yeast cells. This assay offers a platform for studying underlying mechanisms of oligomer Aβ42 induced cell death using gene deletion/overexpression libraries and developing novel agents that alleviate Aβ42 induced cell death.
Keywords: Alzheimer’s disease; Aβ42; amyloid toxicity; autophagy; high-throughput screening; latrepirdine; neuroprotection; oligomer; yeast model.