“Knowing what provokes taupT217 to build up in the brain and how it harms neurons provides new openings for therapeutic intervention,” he said.
Understanding Alzheimer’s
Tau plays important roles in the healthy brain, where, among other things, it helps build and maintain the “microtubules” that serve as highways for transporting important materials within the neurons that form the brain’s circuitry. But in people with Alzheimer’s, tau becomes chemically modified and misshapen in ways that prevent its normal functioning and make it toxic. This eventually leads to two phenomena that account for cognitive decline in Alzheimer’s: destruction of neuronal circuitry and neuron death.
Why this occurs has been only partially understood, but UVA’s new research offers more answers. For example, the researchers found that they could trigger taupT217 buildup inside cultured neurons by exposing them to clusters, or oligomers, of tau. Those are known to accumulate in the Alzheimer’s brain and have long been suspected as a harmful contributor to the disease. They also found that the chemical modification that converts normal tau into taupT217 dramatically decreases tau’s ability to stick to microtubules, which in turn may make it easier for the tau to form toxic oligomers.
“In terms of immediate clinical value, we hope that our findings about the challenge of antibody specificity for measuring taupT217 in blood will quickly resonate with companies that are striving to develop commercially available tests to identify Alzheimer’s patients years before symptoms become evident,” Bloom said. “Because massive irreversible brain damage has already occurred by symptom onset, accurate early diagnosis will be crucial for development of drugs that effectively combat Alzheimer’s.”
