Trickle-Down Theory Challenged

Funds spent chasing a cure for Alzheimer's disease (AD) will advance the field of aging as a whole--at least according to proponents of AD research. Others aren't convinced, and they argue that more money should be funneled directly into basic research on aging.

Ronald Reagan's death from Alzheimer's disease (AD) this month focused public awareness on the plight of those who suffer from this devastating disorder. The attention will undoubtedly garner new money for research on AD. But Richard Miller, a gerontologist at the University of Michigan, Ann Arbor, worries that in a scientific society that already bestows a great deal of support on the disease, a push to fund more AD research could squeeze out other important investigations on the biology of aging. The AD work is worthwhile, says Miller, but the National Institute on Aging (NIA) should channel more money into understanding the science behind the aging process: "There have been hundreds of millions of dollars put into Alzheimer's research, but it has not yet been productive in helping us prevent or reverse [the disease]." If a tiny fraction of that enormous pot had gone into basic-science research, he says, we would be closer to a cure not only for AD but for many other diseases as well.

Neuropathologist John Trojanowski of the University of Pennsylvania in Philadelphia doesn't see it that way. "You can't invest in everything, so you have to prioritize," he says. "Everyone agrees aging is important and that Alzheimer's is important," but investments in AD research have yielded plenty of crucial advances, including targets for drug intervention, whereas basic research is less directed and often produces fewer immediately practical results. Trojanowski and Miller present their cases in this month's SAGE Crossroads Webcast debate.

NIA funnels approximately half of its budget into AD research, and that's no accident, says Richard Adelman, a gerontologist at the University of Michigan, Ann Arbor: "When you're trying to get appropriations from Congress, you need something sexy to sell, and Alzheimer's fills that role." NIA helped secure its overall funding in part by playing up the link between AD and aging: The risk of AD rises sharply with age. "That strategy was brilliant and intellectually justified, but as a result, the overwhelming majority of the congressionally appropriated funds went to Alzheimer's research," says Adelman.

But basic science deserves a bigger piece of the pie, says Miller. "If your goal is to prevent Alzheimer's and prevent breast cancer and prevent blindness, the best thing you could do is support basic-science research into aging. It's the path most likely to help us prevent these diseases," he says. "We've shown in animals that there are ways of slowing the aging process, and when you do that, you dramatically [cut] the risk of many aging-related diseases."

But Trojanowski says that the results of such animal studies might not translate to humans, because mice and rats don't necessarily develop the same aging-related problems--atherosclerosis, diabetes, and AD--that plague elderly humans. And findings in animal studies don't always translate well into human trials. In any case, Trojanowski maintains that research on AD can lead to a deeper understanding of the fundamental mechanisms of aging. For instance, Leon Thal, a neurologist at the University of California, San Diego, says that many of the NIA-funded AD studies at UCSD probe how different neurological processes go awry during the normal aging process. "There is a significant degree of crosstalk [between AD and basic science]," he says.

AD research is the jewel in the crown of NIA's research portfolio, says Trojanowski. "The return on the investment has been one of the more spectacular ones in an NIH research program," he says. Since Reagan was diagnosed with AD in 1994, he says, "we've identified several pathways associated with Alzheimer's, and we have identified targets that, if hit or modified by a drug, could delay onset or slow progression of the disease." Scientists for years have been trying to create vaccines to eliminate or prevent the accumulation of AD's hallmark amyloid plaques, and several drugs are in clinical trials to test whether they can prevent AD (see "Stopping a Mind Thief" ). What's more, researchers have identified genetic links to AD, says Trojanowski. Given these achievements and the tremendous rate at which Alzheimer's research is continuing to proceed, it would be foolish to slow down now, he says.

But those fighting the so-called Alzheimerization of gerontology have no desire to hobble AD research. "What we're pushing for is a greater balance in the NIA's arsenal so that basic research and clinical research are distributed more equitably," says Adelman. Although many scientists have assumed that money pumped into NIA's coffers thanks to public awareness of AD would eventually trickle down to support aging research unrelated to the disease, Adelman says that this hasn't happened. Even the AD studies that provide insights into the aging process do so mostly in the context of the disease, says Miller.

Furthermore, the funding bias is steering scientists toward AD research--and away from studies of the aging process itself, says Miller. And fewer investigators means that the science will advance at a slower pace, a situation that will further impede our understanding of basic biology and disease. "The discovery of oxygen and of the formula for sugar now are seen as fundamental to any understanding of biochemistry, but it took a while," he says. "Similarly, the basic discoveries of aging research, in the last 20 years and the next 30 years, will eventually be seen as fundamental to any understanding of late-life diseases and preventive medicine."

Basic research will certainly help unravel the mysteries behind many diseases, including AD. But it might not churn out results fast enough, says Trojanowski. AD poses an urgent threat. "In 5 or 6 years there will be a tsunami of people turning 65, and that's a time where AD incidence doubles," he says. "About 50% of people age 85 will have AD; those are horrific statistics." Even a discovery that could delay the onset of AD for 5 years would have tremendous benefits, he adds (see "Before We Forget" ). Postponing memory loss will become even more crucial if researchers such as Miller can figure out ways to extend human life span. "No one talks about how wonderful it would be to be demented for 10 or 15 years longer," says Trojanowski. Although both men agree on the destination--long, healthy lives--they will continue to debate the best way to get people there.

Christie Aschwanden is a freelancer working in Boulder, Colorado, where she is waiting for more money to trickle down to writers like her.