Can We Catch Diseases of Aging?

A controversial notion holds that Alzheimer's disease, atherosclerosis, and other chronic illnesses result from infections. If bugs are to blame, we might be able to combat such diseases with antibiotics and vaccines.

Since the discovery of Alzheimer's disease (AD) a century ago, researchers have probed many possible causes for the brain-ravaging illness, from nutrient deficiencies to the aluminum in cooking pans. But if an unorthodox hypothesis proves correct, the cause of AD was right under our noses all the time--or even inside them. According to a growing band of scientists, many of old age's scourges--including atherosclerosis, AD, and some cancers--stem from infections by bacteria and viruses. The evidence so far is inconclusive, but if research confirms the contention, doctors might be able to use the arsenal of antimicrobial weapons to prevent or even treat some of the most dreaded illnesses of old age. But tackling these killers will require the government to take a larger role in creating vaccines, researchers say.

The suggestion that microbes underlie chronic illnesses dates back almost to the discovery that germs cause disease, says evolutionary biologist Paul Ewald of the University of Louisville in Kentucky. Microbiologists gathered the first evidence linking infections to atherosclerosis and ulcers in the late 1800s, and some New York City hospitals were treating ulcers with antibiotics in the 1940s, he says.

But for reasons that researchers don't understand, the idea fell out of favor from the 1950s until the 1980s, when scientists in Perth, Australia, established that a corkscrew-shaped bug called Helicobacter pylori sparked ulcers in the stomach and small intestine. Doctors had previously blamed the painful and sometimes lethal irritations on excess acid induced by stress, bad diet, and other causes, and it took copious evidence and some derring-do to demonstrate that bacteria were the culprits. One researcher went so far as to chug a solution of H. pylori and then cure himself of the resulting infection with antibiotics.

Additional investigations have convicted microbes for several diseases once deemed noninfectious, including liver and cervical cancer. However, age-related ailments such as atherosclerosis, AD, and amyotrophic lateral sclerosis fall into a second category, one for which researchers have garnered suggestive evidence that pathogens are involved.

Of the aging-related diseases, researchers have collected the strongest support that infections trigger atherosclerosis, says molecular geneticist Alan Hudson of Wayne State University in Detroit. And a common lung-invading bacterium called Chlamydia pneumoniae--a cousin of the bug that causes the sexually transmitted disease--might be in the thick of arterial blockage. For example, Finnish scientists detected antibodies against C. pneumoniae in 70% of heart attack patients, a sign that their immune systems responded to the bacterium. Researchers have also excavated C. pneumoniae from the fatty plaques that clog arteries.

Other findings implicate C. pneumoniae in AD as well. In a 1998 study, Hudson, neuropathologist Brian Balin of the Philadelphia College of Osteopathic Medicine in Pennsylvania, and colleagues identified DNA from the bacterium in 17 of 19 brains from AD patients they tested. Only 1 of 19 AD-free brains carried the bug's genes. Balin's group also found that exposing mice to C. pneumoniae spurred formation of protein clumps similar to those that riddle the brains of AD patients.

Finding the same bacterium in such diverse diseases might not be that surprising, says Ewald. People who carry the E4 version of the apolipoprotein E gene have a higher risk not only for AD but for atherosclerosis, stroke, and even multiple sclerosis. And, it turns out, the E4 form also increases susceptibility to C. pneumoniae.

Researchers have snared other suspects, too. For example, work by Ruth Itzhaki of the University of Manchester Institute of Science and Technology in the United Kingdom and colleagues suggests that the herpes simplex 1 virus, which usually causes cold sores, might also contribute to AD. And a bacterium that causes gum disease lurks in artery-jamming plaques.

However, even advocates of the infection hypothesis such as Hudson admit that the supporting evidence is "thin." Critics contend that the C. pneumoniae and herpes viruses in the brains of AD patients might have nothing to do with the illness. They could be bystanders that find diseased tissues congenial but cause no illness on their own. And researchers have uncovered little about how the bugs could spur diseases such as AD, says neuroscientist Mark Mattson of the National Institute on Aging in Baltimore, Maryland.

Amassing definitive data that C. pneumoniae and other bugs incite chronic scourges won't be possible, says Ewald, because the microbes are so much harder to study than, say, the bacterium that causes strep throat. Unlike that germ, many of the suspects in chronic disease resist being isolated in the lab or grown in culture. Even finding the bugs can be difficult, he says, because our methods for flushing out furtive pathogens such as C. pneumoniae, which takes refuge inside body cells, are limited. Moreover, some pathogens might serve as "triggers" for the disease, says Balin. The microbes could ignite illness, possibly by unleashing inflammation, which can progress even if the infections later disappear.

The price of waiting for stronger evidence is high, says Ewald. Chronic illnesses "are the most important diseases--they are killing over half of us." So he advocates loosening the stringent standards for establishing microbial involvement in a disease. If we tentatively accept that viruses and bacteria are culpable, we can deploy our anti-infection arsenal to battle the bugs. Treating everybody with antibiotics would be counterproductive because it would trigger resistance to the drugs. But dosing young patients with lung infections might squelch C. pneumoniae before it infiltrates the brain and blood vessels, says Balin.

But antibiotics aren't going to be a panacea, as a Journal of the American Medical Association report showed earlier this year. The paper weighed results from 11 studies that tested the effectiveness of antibiotics against atherosclerosis and concluded that the drugs don't help. That finding shows that antibiotics can't reverse decades of arterial damage, not that they couldn't prevent chronic illness if taken earlier in life, Balin cautions.

Our best weapons, researchers agree, would be vaccines against C. pneumoniae and other nasties. Not only could the shots prevent infection in young folks, but they might also benefit older patients who already show signs of chronic disease. Because vaccines are not generally profitable for private companies, the federal government will have to step in to develop and distribute the shots, says Mattson. A little prodding from the public might get the bureaucracy moving, says Ewald. That would be a shot in the arm for efforts to prevent the diseases that plague our declining years.

Mitch Leslie, a science writer in Portland, Oregon, is beginning to suspect that Howard Hughes was on to something.