"I Can't Remember"

By Catherine Arnst

Doctors have no way of predicting who is at risk for such debilitating memory loss. They can't even diagnose Alzheimer's with certainty until after the patient's death: It is then that clumps of rock-hard plaque in the brain can be detected during autopsy. This plaque is caused by the buildup of a protein called amyloid, which slowly destroy neurons, starting in the hippocampus. It is unclear whether amyloid is a cause or a symptom of Alzheimer's, but scientists are fairly certain that it starts accumulating 10 to 20 years before mental decline is evident, by which point it is too late to reverse the process.

The current Alzheimer's treatments are an act of despair," says Dr. Eric R. Kandel, professor of psychiatry at Columbia University. "We have to start [intervening] much earlier if we want to make a difference." Ergo the focus on early memory loss, when the brain may still have a chance to save itself. Success in this area will owe much to the study of animals that likely have far less to remember than humans. It seems that brains of insects, apes, and people work in much the same way. Kandel shared the 2000 Nobel prize for medicine for his breakthrough discoveries about memory that grew out of painstaking work with sea slugs. Kandel's discoveries were amplified by Tim Tully, a fellow of Cold Spring Harbor Laboratories on Long Island, whose research is based on the brains of fruit flies.

Work on these two lowly life forms led to a revolution in the understanding of memory. Kandel discovered that a neurotransmitter called cyclic-amp, or CAMP, plays a key role in strengthening synapses. Camp activates a protein called CREB, which in turn switches on the genes that control the release of neurotransmitters essential to long-term memory. "Think of CREB as a general contractor that organizes the cascade of genes that build memories," says Tully. Once CREB was discovered, Tully went to work designing a strain of fruit flies with the CREB protein permanently activated. The result: flies with photog

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