Abstract:

The 42 amino acid peptide known as amyloid beta (or Aβ) has been implicated as the most likely causative agent of AD since its discovery in plaques in 1985. Since then evidence has accumulated to support the association between AD and amyloid beta. However, progress to find a cure for AD has been very slow, due to lack of reliable models and a lack of understanding about what role amyloid beta plays in AD. The failure to cure AD led many to doubt that amyloid beta should be the prime target for the treatment of AD, resulting in a backlash against research on amyloid beta as a drug target. The recent antibody trial is showing some promise, although it did not meet the desired end points. There is growing interest in naturally derived compounds as chemo preventatives to remove amyloid beta. Such compounds should be taken conveniently, which means it is best if they can be ingested. Epidemiology suggests there are many compounds in existing foods that may be useful for chemo prevention of AD. Since we have reasonable ideas about the molecular basis of amyloid beta it is important that we incorporate these ideas into rationale screening for AD chemo preventatives. The ability of yeast to be used as a tool for screening anti amyloidogenic compounds is a useful and unique contribution. It can be adapted to high throughput use, it informs about compounds that are bioavailable, and it requires no amyloid beta preparation. In a world that seeks new ways to lower amyloid beta, the yeast assays should be valuable additions to moving forward.