Most current methods for diagnosing Alzheimer’s and MCI rely on cognitive tests that assess skills such as memory or problem solving. But scientists are aiming for more precise—and much earlier—detection. Some of the most promising techniques for early diagnosis rely on positron emission tomography (PET). By combining this basic technique with amyloid imaging agents such as Pittsburg Compound B (PiB) or FDDNP, researchers have been able to detect Alzheimer’s markers in those with only mild cognitive impairment. In the United States, the work has received a significant boost from the Alzheimer’s Disease Neuroimaging Initiative, a public-private partnership driven by the federal National Institute on Aging. The six-year program, launched in 2004, brings about $60 million to the study of imaging and other biomarkers, such as A-beta levels in blood or cerebrospinal fluid, in diagnosing Alzheimer’s disease.

 

“I don’t think we’re going to use the word ‘cure,’ says Dr. Susan Molchan, until recently ADNI’s program director. “But we hope to slow the progression of Alzheimer’s. The hope is the earlier you get that, the more you can maintain people at a higher level of function longer.”

 

UCSF’s Boxer, for example, focuses his research on brain imaging that would detect the buildup of A-beta long before a person falters on a cognitive test. At the Mayo Clinic’s division in Jacksonville, Florida, leading A-beta researcher Younkin is working on blood or spinal fluid tests that would track a person’s levels of different A-beta fragments, looking for telltale ratios linked to increased Alzheimer’s risk. He hopes, in the future, that A-beta testing becomes as routine as a cholesterol screen.

 

“You would draw plasma, or tap their cerebrospinal fluid, and see what’s happening with their A-beta ratios,” Younkin says. “If you see a certain ratio, that’s a pretty good predictor. Then maybe you want to do a brain scan. You confirm there is amyloid in the brain. At that point, you initiate therapy.”

 

Analysts say Alzheimer’s imaging technologies could launch commercially by 2011, shortly after at least one of the drugs now in Phase III trials is expected on the market.

 

The amyloid hypothesis has a significant head start in driving Alzheimer’s research and drug development, but different approaches to A-beta, genetic factors, tangles of nerve fibers, and a nerve-cell building block called tau are also worthy of investigation. 

 

At the Buck Institute for Age Research, scientists have created a strain of mice with brains packed with A-beta plaques. But the rodents show no sign of memory loss. Buck scientists say that is because the signaling process between brain cells is still intact, despite the presence of plaques. According to Bredesen, the research demonstrates that Alzheimer’s is more a disease of brain signaling than A-beta toxicity. Beyond better understanding the intricacies of A-beta, however, he hopes the scientific community will uncover much broader findings about this increasingly prevalent illness.

 

“Why is Alzheimer’s so common? Are we going to find viruses associated with this? Will it have a big dietary component?” Bredesen asks. “I think the next five or 10 years will be extremely interesting, and not just because we have ways to slightly reduce A-beta.”

 

Within the next decade or two, says Wyeth’s Pangalos, “We’ll know whether the amyloid hypothesis is right. If it is, we’ll have disease-modifying drugs. If not, we’ll still be trying to treat symptoms.”

 

The Mayo Clinic’s Younkin calls Alzheimer’s “the most major devastating disease of aging.” “The reason it’s so frightening is that it attacks what is uniquely you,” says William Thies, vice president of medical and scientific relations for the Alzheimer’s Association. “You can have four or five heart attacks and you walk down the street and you still look like you. As you begin to attack someone’s personality, you attack who they really are.”

 

As insurance against those bleaker prospects, Alzheimer’s disease scientists and advocates are pushing hard to boost federal funding for Alzheimer’s research, which rang in at a relatively paltry $645 million in 2007. A bill now before the U.S. Senate would pump up that amount over the next five years, hitting $1.3 billion by 2012. This money, advocates say, is essential to basic research that won’t translate easily into big drug profits. And if the new drugs can hold the line against Alzheimer’s, the Alzheimer’s Association’s Thies also sees a need for new rehabilitative medicine, similar to the therapies stroke patients receive to restore speech or movement.

 

“The next few years are going to be very important,” Thies says. “We will look at them as having been a bit of a turning point. We are in the early stages of an epidemic, and we have to do something now.”