Fantastic Four

After studying Alzheimer’s disease for 16 years, Karen Hsiao Ashe wasn’t surprised when her own father began showing signs of the disease last year.

“My father is 90 years old, so his dementia is a sad fact of statistics,” Ashe says. “About 50 percent of people over the age of 85 have the disease.”

Ashe wants to change that with preventive medicine. Unless researchers stop its development, the next 40 years will see 28 million new cases of Alzheimer’s disease in this country. Alzheimer’s progressively impairs cognitive function and memory by destroying synapses that convey signals between neurons in the brain, then neurons themselves. Most patients die after about 10 years.

“I chose this area of research because it’s the most important unresolved medical problem facing our country [and] the world,” Ashe says. To explain her focus on prevention, she draws a comparison with polio. “Had a vaccine not been developed for polio, hospital wards would now be filled with people needing artificial ventilators to breathe. Similarly, not only is treatment of Alzheimer’s likely to be less effective than prevention, it’s also likely to be 10 to 1,000 times more expensive.”

But there can be no preventive mechanism until researchers know precisely what to prevent. Ashe is examining Alzheimer’s disease at a molecular level, looking at genetic markers and the way proteins interact with the neurons of the brain. Mounting evidence shows that Alzheimer’s-related changes develop in the brain long before the dementia can be diagnosed. Those changes distinguish the disease from other cognitive decline that can come with normal aging and make Alzheimer’s difficult to diagnose.

“The specific genes influencing ‘sporadic Alzheimer’s’”—the most common form of the disease—“have not been identified, except for the APOE e4 gene [apolipoprotein e4],” Ashe says, but “there are probably a handful, maybe even a dozen or more.” Also, APOE e4 indicates only susceptibility to the disease, not the presence of the disease itself. “The more copies of APOE e4 you have, the higher the risk you are for Alzheimer’s disease. However, you could have two copies of APOE e4 and live to be 95 and still not get Alzheimer’s,” she adds.