A study from the Buck Institute for Age Research offers a revolutionary new model for Alzheimer's disease (AD), a devastating neurodegenerative disorder which afflicts 24 million people worldwide. In an effort to unravel the normal function of a protein implicated in AD, scientists in California and France have discovered a naturally occurring protein that provides a new therapeutic target for the disease. The finding upsets the current theory that AD is a disease of toxicity stemming from damage caused by sticky plaques that collect in the brain this research points to the condition as a disorder involving an imbalance in signaling between neurons. The study appears online in the Nature publication Cell Death and Differentiation.
One of the mysteries of AD has been the normal function of the amyloid precursor protein (APP) which are concentrated at the points where neurons connect. Even though the sticky amyloid plaques which have been viewed as a hallmark sign of AD result from APP, it seems unlikely that APP exists simply to cause Alzheimer's disease. In their study, scientists from the Buck Institute and the CNRS (Centre Nationale de la Recherche Scientifique) show that APP binds to netrin-1, a protein that helps to guide nerves and their connections in the brain, as well as helping nerve cells to survive. When netrin-1 was given to mice that have a gene for Alzheimer's disease their symptoms were reversed, and the sticky amyloid was reduced. These results suggest that the long-held belief that AD is caused by brain cell damage inflicted by the amyloid plaques may be wrong; instead, it is beginning to appear that the disease stems from an imbalance between the normal making and breaking of connections in the brain, with netrin-1 supporting the connections and the amyloid breaking the connections -- both by binding to APP and activating normal cell programs. Not only did the netrin-1 binding to APP keep the nerve cells alive and connect
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Buck Institute for Age Research