Dr. Eric Reiman, clinical director of TGen's Neurogenomics Division and executive director of the Banner Alzheimer's Institute, explained that tau holds together the skeleton inside neurons. When phosphate molecules stick to tau proteins, the skeleton falls apart and the neurons begin to retract their synaptic branches and die, leading to memory loss and thinking problems.

In this study, researchers used a molecular tool called siRNA to screen the entire human genome, said Dr. Reiman, a co-author of the scientific paper. This tool enabled the TGen-led team to discover which proteins, when genetically turned off, prevent phosphate molecules from sticking to tau. The three kinases, or proteins, that appear to contribute to the formation of brain tangles, can now be targeted by protein-inhibitor drugs.

"This study used a powerful tool to discover three proteins that may be involved in tangle formation. If safe and well-tolerated tangle-busting medications can be developed, they offer great promise in the treatment of Alzheimer's disease,'' said Dr. Reiman, who also is Director of the Arizona Alzheimer's Consortium.

The next step will be to identify drug compounds that can negate the effects of the three kinases linked to tau hyperphosphorylation.

"The reason that we did this study was to identify therapeutic targets for Alzheimer's disease, whereby we could modify the progression of tau pathology,'' Dr. Dunckley said. "This was a screen to identify what the relevant targets are. Now, we want to match those targets to treatments.''

Source: The Translational Genomics Research Institute