The team has now found that LTD enhancement in the -amyloid-producing flies is due to increased activity of PI3-kinase. A reduction of this activity via injections of PI3 kinase-blocking drugs or by switching off the gene that encodes PI3 kinase both restored normal LTD signals. With these measures, the team not only improved memory in aging fruit flies, but also decreased the buildup of -amyloid deposits.

These findings on -amyloid's effect on PI3 kinase activity might explain another mystery about the disease. Among patients, the disease is sometimes known as "brain diabetes" because brain tissue gradually becomes resistant to insulin, further impairing brain function. Insulin is one of the molecules that normally induce PI3-kinase activity, which in turn mediates the cell's response to insulin.

"Our results now suggest that the Alzheimer's brains might become insulin-resistant because PI3 kinase activity is already at the maximum due to its activation by -amyloid and therefore is no longer able to respond to insulin," explains Zhong. "It might be possible to tackle these various disease symptoms by targeting PI3 kinase."

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