Under normal circumstances, the tau protein is a hard-working participant in memory and normal brain functioning. But as is becoming increasingly evident, in Alzheimer's disease and other neurodegenerative diseases, tau not only ceases to play a productive role in brain health, but actually undergoes a Jekyll-and-Hyde transformation to become a misshapen villain that destroys brain cells.
Now, a novel antibody technology developed by a scientific team at Beth Israel Deaconess Medical Center (BIDMC) provides the first clear distinction between two tau isoforms - one healthy and one disease-causing - and demonstrates that only the disease-causing isoform is found in the neurons of Alzheimer's patients and is exhibited at a very early stage of disease. Described in the March 30, 2012 issue of the journal Cell, the findings raise the intriguing possibility that the development of antibodies and vaccine that target only the disease-causing tau isoform could be used to diagnose, treat and potentially even prevent Alzheimer's before the onset of debilitating symptoms.
"Since Alzheimer's disease takes at least a decade to develop, the major challenge to halt memory loss is to identify the initial period when the tau protein is transformed from 'good guy' to 'bad guy," explains co-senior author Kun Ping Lu, MD, PhD, an investigator in the Division of Hematology/Oncology at BIDMC and Professor of Medicine at Harvard Medical School (HMS). "By developing an innovative approach to making antibodies, we have uncovered a new strategy to specifically remove disease-causing tau, while leaving health tau intact to carry out its important responsibilities."