NIH supports Buck Institute’s Innovative Alzheimer’s Research with $1.6 Million “EUREKA” Grant

The Buck Institute for Age Research has received a $1.6 million dollar “Eureka” grant from the National Institutes of Health to further its innovative research in Alzheimer’s disease. The highly competitive grant was awarded to Buck faculty member and founding CEO Dale Bredesen, MD. Last year the NIH funded just 38 Eureka grants nationwide.

The “Eureka” grant stands for Exceptional, Unconventional Research Enabling Knowledge Acceleration. The awards go to scientists proposing innovative, even controversial research that could provide a paradigm shift in dealing with a difficult biomedical problem. An estimated 5.2 million Americans have Alzheimer’s, with those numbers expected to soar as the population ages. There is no effective treatment for the neurodegenerative disease.

Research in the Bredesen lab focuses on Alzheimer’s as a brain signaling disorder that impacts brain plasticity, rather than the current dogma that Alzheimer’s is a disease of toxicity stemming from damage caused by sticky amyloid plaques that collect in the brain.

“We are very excited to receive this award,” said Bredesen. “It points us in a new direction in Alzheimer’s research, which is essential if we are to find an effective treatment for this devastating disease.” Bredesen says over 50,000 scientific papers have been published on the amyloid plaque theory of the disease, offering no explanation for the production or function of the amyloid beta peptide, which occurs in normal cells.

Initial studies in the Bredesen lab support the theory that Alzheimer’s is a nerve signaling disorder.  Research in the Bredesen  lab focuses on netrin-1, a naturally occurring protein that helps to guide nerves and their connections in the brain, as well as helping nerve cells to survive. Netrin-1 interacts with the amyloid precursor protein (APP) which is concentrated at the points where neurons connect. Even though the sticky amyloid plaques which have been viewed as a hallmark sign of Alzheimer’s result from APP, Bredesen says it seems unlikely that APP exists simply to cause the disease. In previous studies, Bredesen and colleagues showed that APP binds to netrin-1. When netrin-1 was given to mice that have a gene for Alzheimer’s  their symptoms were reversed, and the sticky amyloid was reduced.

One surprising implication of this new theory is that Alzheimer’s is a “prionic” disease – a distant, yet not necessarily contagious, cousin to Mad Cow Disease.  Prions are proteins that occur normally in a harmless form. When the protein folds into an aberrant shape, the normal prion turns into a rogue agent. It then co-opts other normal prions to become rogue prions as well. Bredesen says studies are now underway to determine if netrin-1 is an “anti-prion.

“Since there is still no truly effective therapy for Alzheimer’s, it is critical that alternative models such as this be explored, and their tenets and implications confirmed or refuted,” said Bredesen.  “Furthermore, research in this area may ultimately lead to new insights into other neurodegenerative diseases, such as Parkinson’s and amyotrophic lateral sclerosis, as well.”