A small group of scientists, including some in Philadelphia, have been bucking the research establishment for years by arguing that microbes might trigger the deadly form of dementia in older people. They contend that their ideas deserve more respect — and money — now that years of attempts to attack Alzheimer’s disease by focusing research and medications on its hallmark signs in the brain — clumps of amyloid called plaques and misshapen tangles of tau — have so far failed to produce a good treatment.
“It does not appear that therapeutics based on tau and amyloid are going to work,” said Brian Balin, a neuropathologist who directs the Center for Chronic Disorders of Aging at Philadelphia College of Osteopathic Medicine, and has been studying the role of the Chlamydia pneumoniae bacteria in Alzheimer’s since 1998. “Is this really the problem? It’s more of an end result, many of us think.”
Balin organized the first scientific meeting on the pathogen hypothesis theory of Alzheimer’s in Philadelphia in October 2014. There were eight speakers. The follow-up meeting, which posited that Alzheimer’s is a “chronic inflammatory disorder,” was held this October in Switzerland and drew 24 speakers. Balin was also among more than 30 scientists who signed an editorial in the Journal of Alzheimer’s Disease in 2016 calling for more research into the connection between infection and Alzheimer’s. It is not clear, they said, whether plaques and tangles are causes or consequences of disease. There was evidence that the process may start with various viruses and bacteria. Some microbes, they said, may remain latent in the body for years.
Asked if the group’s ideas are getting more respect, Balin replied with a laugh, “I don’t know if it’s better accepted. We don’t have people railing against it.”
New work is indeed bolstering the idea that microbes could play a role in starting the cascade of brain changes that lead to cognitive decline. A recent Mount Sinai and Arizona State University study, for example, found that the brains of people with Alzheimer’s disease contained more of two types of herpes viruses — HHV-6 and HHV-7 — than the brains of people without dementia. Harvard University researchers have found evidence, in lab studies and mice, that amyloid clumps are part of the body’s innate, or most primitive, immune system.
In earlier studies, Balin found chlamydia disproportionately in brains of Alzheimer’s patients. Other studies implicate the herpes virus that causes cold sores. (Sexually transmitted forms of chlamydia and herpes are not suspects.) Judith Miklossy, director of the Prevention Alzheimer International Foundation and International Alzheimer Research Center in Switzerland, says the pathology in brains of people with late-stage syphilis is virtually indistinguishable from that in Alzheimer’s. She has also found Borellia burgdorferi, which causes Lyme disease, in the brains of Alzheimer’s patients and was able to induce Alzheimer’s pathology with it in cell culture. Infection with HIV, the virus that causes AIDS, is known to increase the risk for dementia, even when it’s suppressed by medications.
Other experts caution that the science is not yet strong enough to prove germs are the cause or, more likely, one of the causes of dementia. And because several of the germs found more frequently in the brains of people with Alzheimer’s are ubiquitous, scientists suspect that if they are involved, they are likely part of a complex interplay of genes, age, inflammation, environmental exposures, head trauma, and metabolic factors.
“It is clear that there are more and more data being accumulated that point to a connection of some kind between viral sequences and Alzheimer’s in the brain,” said Richard Hodes, director of the National Institute on Aging. He added, however, that a correlation between the presence of microbes in the brain and Alzheimer’s pathology does not prove one causes the other.
Eliezer Masliah, director of the NIA’s division of neuroscience, said the agency is funding research into potential treatments from “multiple directions.” It has targeted funding for how the body’s microbiome affects the nervous system and why people with HIV are at higher risk for dementia. Hodes said the NIA will consider whether to make research on germs and Alzheimer’s a higher priority during the next round of funding.
Private funders intrigued by the infectious-disease hypothesis have already stepped in. In 2017, Leslie Norins, a doctor who became a medical publisher, offered a $1 million prize to anyone who can identify an Alzheimer’s germ. He’s also supporting the Infectious Diseases Society of America with two $50,000 grants to study in