In Alzheimer’s disease, two kinds of abnormal structures accumulate in the brain: amyloid plaques and neurofibrillary tangles. The plaques contain fibrils that are made from protein fragments called “beta-amyloid peptides.” The tangles also are fibrous, but they are made from a different substance, a protein called “tau.”
In the new study, the researchers found a deadly connection between beta-amyloid and tau, one that occurs before they form plaques and tangles.
According the researchers, this connection causes the swiftest, most sensitive and most dramatic toxic effect of beta-amyloid found so far.
This connection between beta-amyloid and tau breaks apart microtubules – highways along which “synapse” replacement parts move rapidly in the nerve cell from where they are made to where they are needed.
Synapses are connections between nerve cells, and in the brain they are the structural basis of memory and cognition. When nerve cells in the brain lose their microtubules synapses disappear. The loss of synapses, and consequent loss of memories and cognitive skills, cannot be reversed, and can lead directly to nerve cell death.
“We think we’ve found one of the seminal cell biological events in the pathogenesis of Alzheimer’s and if we can figure out all of the steps in the process and understand each player at every step, it will represent many potential new drug targets for Alzheimer’s therapy,” commented George Bloom, professor of biology and cell biology at the University of Virginia.