There is a general consensus that extracellular amyloid-beta (Aß) plaques are the villains that cause Alzheimer's disease and the death of neurons. But, other than identifying amyloid-beta in a lineup, that's about all that is known about these criminal peptides. Not much can be said about what makes them tick. Now, researchers at the University of California Santa Barbara think they have discovered the mechanism by which these plaques destroy cells, giving some hope for new areas of inquiry for a cure.
Stuart Feinstein, co-director of UCSB's Neuroscience Research Institute, has spent the last three decades studying a protein called tau, found in the long axons of neurons, which normally connect neurons with their targets. But tau, apparently, has a dark side, as well. The ability of amyloid beta to kill neurons requires tau. So, Feinstein and colleagues set out to discover how tau is turned into something so bad by amyloid beta.
Feinstein explains in a release that most Alzheimer's researchers believe amyloid beta causes tau to become abnormally and excessively phosphorylated, meaning they become inappropriately chemically modified with phosphate groups. So, that was Feinstein's belief going into the research.
It was wrong. Actually, what happened is that amyloid beta fragmented tau and then killed the cell within 24 hours. "We all like to get a curve ball tossed our way once in a while, right?" Feinstein said in the release. "You like to see something different and unexpected."
So, now there's an entire new area of inquiry going on in Alzheimer's disease. Feinstein said he believes that if tau is destroyed, the cell's cytoskeleton fails, too, resulting in cell death. But it will take time to study all the implications.
- read the release from UCSB
- and the abstract in The Journal of Biological Chemistry
Special Report: Making sense of the Alzheimer's drug pipeline