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Quick, high-volume test offers fast track in search for Alzheimer's drugs
Date:11/15/2012

orking with E. coli, a standard laboratory bacterium, Hecht said.

For the current research, Hecht and his co-authors examined 65,000 randomly chosen organic compounds that Chen acquired from the Broad Institute of the Massachusetts Institute of Technology and Harvard University. The technique revealed 269 compounds that halted the buildup of Aβ42 aggregates. Of those, Fortner McKoy selected the eight most readily available for further testing. Fortner McKoy found that D737 best prevented the accumulation of Aβ42 and reduced mortality in cell cultures. In addition, the researchers found that the compound reduced the production and accumulation of reactive oxygen species, which damage cells.

The researchers then tested the compound on healthy fruit flies with no Aβ42 accumulation, as well as on flies with a regular human-form Aβ42 gene and flies with a mutant gene which is found in some humans with Alzheimer's that causes extra buildup of the peptide. For each of these three fly types, one group of flies did not receive D737 while another group was given the compound in concentrations of 2, 20 or 200 micromolar.

In the flies with regular and accelerated Aβ42 buildup, those receiving D737 lived an average of four to six days longer than similarly altered flies that were not fed the compound. The healthy fruit flies that received D737 showed no change in lifespan, demonstrating that the compound is non-toxic in fruit flies, Hecht said.

To test mobility, the researchers put 20 flies from both of the genetically altered groups into the bottom of a vial and recorded how many had climbed to the top. After 38 days, only 6 percent of untreated flies with normal Aβ42 accumulation could climb, as opposed to as many as 34 percent of the flies receiving D737.

In flies with the mutant Aβ42 gene, all those left untreated lost mobility after 27 days. Of those given the compound, however, 50 to 78 perce
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Contact: Morgan Kelly
mgnkelly@princeton.edu
609-258-5729
Princeton University
Source:Eurekalert  

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