Validation of Folate in a Convenient Yeast Assay Suited for Identification of Inhibitors of Alzheimer's Amyloid-β Aggregation

Abstract

Previously in the search for chemopreventatives for Alzheimer's disease (AD), microbial cells with amyloid-β (Aβ) protein fusions have been used to screen for compounds that reduce the aggregation, misfolding or oligomerization of Aβ. In the current study, such a system has been used to look at the effect of folate, whose deficiency has been associated with AD. A folate-deficient yeast strain producing Aβ fused to green fluorescent protein (GFP) that spontaneously misfolds/aggregates and suppresses green fluorescence was used to examine the effects of folinic acid on Aβ-GFP fluorescence. At levels that did not affect growth or plasmid stability, increasing levels of folinic acid led to increasing green fluorescence, suggesting folate can assist with preventing Aβ-misfolding/aggregation. This result supports a protective role for folate and suggests that yeast assays may provide significant new approaches for testing of AD chemopreventatives.