Most of the drugs being tested to treat or prevent Alzheimer's disease target proteins called beta amyloid, which accumulate in the brain and are suspected as a cause of the devastating dementia.
But new research in mice suggests another treatment approach -- reducing levels of a protein called tau. Tangles of this protein have long been observed in brains of Alzheimer's patients, but its role in the disease and connection to beta amyloid plaques are unclear.
In the new experiment published in Science last week, scientists reported that they reversed memory loss in mice with simulated Alzheimer's and prolonged their lives by modifying their genes to make less tau.
" The mice were able to solve maze and memory tasks beautifully, even at an advanced age," said Dr. Lennart Mucke, director of the Gladstone Institute of Neurological Disease in San Francisco and a leader of the work. He said this finding could lead to a tau-based treatment that makes "the brain more resistant to the poisonous actions" of proteins gone bad.
Mucke warned that there are many steps before the strategy used in the mouse experiment can even be tried in people. Tau is an essential protein that allows movement of nerve impulses. The mice showed no harmful effects. Yet, scientists must proceed very cautiously when tinkering with genes in people. There have been some cases of learning disabilities in people who have a small natural deletion in the part of the genetic code that contains the tau gene -- although scientists aren't sure if it was the tau gene or another one.
Mucke said there are other ways to reduce levels of tau that could be tried. Researchers have found some substances, which have been tested in human cells, that degrade tau after it is produced .
Dr. Dennis J. Selkoe, a leading Alzheimer's researcher at Brigham and Women's Hospital and director of a company working on amyloid-based treatments, said targeting tau could be a useful alternative if work on amyloid fails or if tackling the disease requires a one-two punch. He also said Mucke's work is important for the light it sheds on how the disease works -- that beta amyloid seems to be destructive only in the presence of tau.
"This addresses one of the missing links in Alzheimer's disease," said Selkoe, a neurology professor at Harvard Medical School. "This could help resolve why some patients with a lot of beta amyloid in the brain don't have much . . . cognitive impairment."
The Gladstone scientists also found that normal tau -- not just the abnormal tangles -- seemed to facilitate the damage. They found that reducing levels of tau also protected the mice against seizures and other problems in which brain cells go into overdrive. Since that kind of overstimulation is involved in Parkinson's and Lou Gehrig's among other diseases, Mucke said, the new work may have even broader applications.