Genetic Discoveries Are Only Part of the Alzheimer’s Research Puzzle

For decades, scientists have shared Bob Cimiano’s frustration. Back in 1988, “I was ready to quit and work on something else,” says Dr. Sangram S. Sisodia, chairman of the departments of neurobiology, pharmacology and physiology at the University of Chicago and one of the nation’s top Alzheimer’s researchers. “Then they discovered the gene.”

In the last decade, scientists actually have discovered four genes linked to the creation of the plaques and tangles that characterize Alzheimer’s disease, three of them linked to onset of the disease before age 60. Sisodia expects that many more genes that contribute to the disease remain to be discovered.

One way to look at these genes is as molecular cue balls, each one producing a protein that sets off a different biochemical chain reaction, which ends up producing Alzheimer’s telltale signs.

By tracing those chain reactions, scientists now have many places to try to intervene in the process and halt the formation of plaques and tangles, Sisodia says.

Already, scientists have been able to develop vaccines that have reduced the plaques in the brains of mice.

“What happens once we start dissolving plaques in humans?” Sisodia asks. “Maybe the patient doesn’t get better, but at least we stabilize the patient and change the clinical course of the disease.”

Yet there is a nagging doubt in some scientists that it isn’t plaques and tangles that cause the behavioral problems afflicting Alzheimer’s patients, but some as-yet-undiscovered agent that destroys the brain cells.

“We still don’t know what kills neurons,” says Dr. Jung H. Kim, associate professor of pathology at Yale University School of Medicine in New Haven, Conn. “The fundamental thing is preventing the death of neurons. How to prevent that, nobody knows.”

Kim believes there won’t be an effective treatment for Alzheimer’s for decades.

Dr. Thomas Bird, a neurologist at the University of Washington who has studied early onset Alzheimer’s in dozens of families descended from Germans who settled near the Volga River in the 1800s, agrees that the exact mechanisms that destroy brain cells have been elusive.

However, he remains much more optimistic that the answer lies somewhere along the pathways scientists have been exploring.

“My attitude has changed in the last two years. These are quite exciting days,” Bird says. “I think there is the potential for new treatments.”

Bird, for instance, has found a clear correlation between a gene called presenilin 2 and the early onset of Alzheimer’s in the German families he studied.

“But there are absolutely many cases of early onset with no family history,” Bird says. “It is a great puzzle.”