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Saving the Good Guys

Antibody tool could aid efforts to treat, diagnose Alzheimer’s

Under normal circumstances, the tau protein is a hard-working participant in memory and brain functioning. But in Alzheimer’s and other neurodegenerative diseases, tau ceases to play a productive role in brain health and instead transforms to become a misshapen destroyer of brain cells.

Until now, distinguishing between the Jekyll and Hyde forms of tau has been challenging. But a new antibody technology developed by an HMS research team at Beth Israel Deaconess Medical Center can differentiate between the healthy tau isoform and the disease-causing one. In addition, it has demonstrated that only the disease-causing isoform is found in the neurons of Alzheimer’s patients and that it is exhibited at a very early stage of disease. Described in Cell’s March 30 issue, the findings raise the intriguing possibility that antibodies and vaccines developed to target only the disease-causing tau isoform might be used to diagnose, treat, and potentially even prevent Alzheimer’s.

“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,’ ” says co-senior author Kun Ping Lu, an HMS professor of medicine and an investigator in Beth Israel’s hematology and oncology division. “We have uncovered a new strategy to specifically remove disease-causing tau, while leaving healthy tau intact to carry out its important responsibilities.”

Alzheimer’s affects 5.4 million people in the United States and more than 30 million people worldwide. As the baby-boom generation ages and life expectancies continue to increase, these numbers are expected to rise dramatically, with some estimates projecting that by 2050 Alzheimer’s will affect 120 million people worldwide. There is currently no effective treatment for the disease.

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