A study from Drexel researchers offers new evidence to support a controversial hypothesis: Alzheimer’s disease results from the body’s inflammatory response to chronic infections. The scientists believe that bacteria create slimy, impenetrable biofilms in the brain, prompting the immune system to destroy surrounding tissue. This intriguing idea — though supported by a growing body of documentation — is still contested by many in the scientific community.
Losing the Trail
Alzheimer’s affects 5.3 million Americans and is the sixth leading cause of death in the United States. It is the only one of the top ten killers that cannot be prevented, cured or slowed. In 2015, Alzheimer’s and other dementias cost the nation $226 billion. By 2050, these costs could rise to $1.1 trillion, according to the Alzheimer’s Association.
The disease is characterized by plaques in the brain, which form when sticky protein pieces called beta-amyloid clump together. Despite billions being invested to understand how the beta-amyloid contributes to a slow, cognitive decline, the disease remains a mystery.
“We have done absolutely nothing to change the course of the disease. Other chronic diseases, we have affected, because we understand their etiology — what causes them,” says Garth Ehrlich, PhD, a professor in the College of Medicine and director of the Center for Genomic Sciences. “There is nothing new you can do for an Alzheimer’s patient that you couldn’t do 20 years ago.”
Dr. Ehrlich and other Drexel faculty members are among a group of scientists who think the direction of Alzheimer’s research needs to be rerouted.
“The lack of progress in Alzheimer’s research suggests that the etiological hypotheses followed by the mainstream scientific community are either wrong or incomplete,” Ehrlich says.
A Novel Theory
In the early ’90s, pathologist Alan MacDonald theorized that Alzheimer’s disease may have a bacterial component. Later, Swiss researcher Judith Miklossy made a profound observation when she showed that neurosyphilis (a bacterial disease of the brain) and Alzheimer’s were essentially identical.
Miklossy and her colleagues found two types of spirochetes (long, corkscrew-shaped bacteria) in the brains of more than 90 percent of Alzheimer’s disease patients: Borrelia burgdorferi, which causes Lyme disease; and periodontal pathogens that are a close relative of syphilis. Studies from other researchers have made similar connections between bacteria and dementia.
The findings intrigued Herbert Allen, MD, chairman of Drexel’s Department of Dermatology, who has treated patients with both Lyme disease and syphilis.
In a 2014 study, Allen showed that eczema may be caused by biofilms — multicellular assemblages of bacteria that exude slimy, glue-like substances. Once bacteria metamorphose into a biofilm, antibiotics can no longer treat them. The 2014 study proposed that staphylococcal bacteria that live on the skin produce a biofilm that blocks sweat ducts, activating the immune system, which causes itching and irritation.
Allen’s newest study, published this week in Neuroinfectious Diseases, suggests that spirochetes in the brain could be operating in the same way to cause Alzheimer’s.
Allen and a team of scientists investigated seven post-mortem brains of Alzheimer’s disease patients, comparing them to 10 control samples from people who had died from other causes.
In each of the Alzheimer’s brains, the researchers saw what they believe to be biofilms. The researchers also identified a protein called TLR 2, which plays a key role in activating the body’s innate immune system.
According to Allen’s hypothesis, the spirochetes enter the brain during a dental procedure or after a person contracts Lyme, and then spin out a protective biofilm. The body’s first responders try to clear the infection, but immune cells cannot penetrate the biofilm matrix that encases the organisms. Instead, the immune system ends up destroying the surrounding tissue. This is exactly what happens in cystic fibrosis.
“So it’s neither the infection, nor the biofilm, nor the beta amyloid that causes the disease, but the body’s own immune system,” Allen says.
As for why Alzheimer’s primarily strikes older adults, the study’s authors note that spirochetes take 90 days to divide, so the process takes a long time to build up sufficient numbers of organisms to form a biofilm. However, after someone suffers a stroke, the adaptive immune system — which the authors liken to a “machine gun” — is activated and eradicates organisms with much greater efficiency than the innate immune system.
“However, just as in the situation with the innate immune system, it cannot penetrate the biofilm either, thus it destroys greater amounts of the surrounding neural tissue much more rapidly,” the researchers write.
The hypothesis could explain why symptoms of dementia can appear suddenly after a stroke, rather than slowly over time, as is observed with traditional Alzheimer’s patients.
A Paradigm Shift
Further research will be needed to confirm that spirochetal bacteria (or any bacteria for that matter) can trigger the inflammatory cascade that leads to Alzheimer’s disease. Some experts note that the sticky substance seen in the brain tissue sections from Allen’s study could actually be the beta-amyloid, rather than the presence of biofilms.
However, Allen’s observations add fuel to a growing body of data that makes the connection between bacteria and Alzheimer’s.
Ehrlich (who was unaffiliated with Allen’s study), is one of the world’s leading experts in biofilms. He has dedicated his career to trying to understand how bacteria cause chronic disease, and he agrees that testing the hypothesis that biofilms play a triggering role in Alzheimer’s is a worthwhile pursuit.
In his lab, he is conducting a blinded study of brains from both Alzheimer’s patients and controls in which multiple DNA tests are being used to first identify and then confirm the presence of any bacteria. The researchers will then determine which genes the bacteria are expressing by performing species-specific RNA analyses.
If their hypothesis is confirmed, the findings could shift the paradigm of Alzheimer’s disease research. Rather than developing drugs to try and target the beta-amyloid (as is the direction of most current studies), researchers could be putting efforts into developing more reliable tests for bacterial detection in the central nervous system and investigating new anti-biofilm treatments.
As for why funding agencies and other scientists have been largely unappreciative of the “bacterial” Alzheimer’s hypothesis, Ehrlich defers to a quote from German physicist Max Planck: “Science advances one funeral at a time.”
“Scientists are supposed to be the most open-minded people in the world, but many of them are not,” Ehrlich says. “From my perspective, people should go into science to be very open-minded and to test any valid hypothesis. And certainly not stand in the way of people who want to test something you don’t think is right.”
Media interested in talking with Ehrlich or Allen should contact Lauren Ingeno at 215.895.2614 or lmi28@drexel.edu.
