Nikki Schultek, founder of the global medical research consortium Intracell Research Group, takes a close look at how the COVID-19 pandemic may prompt a much-needed shift in perspective for the infection hypothesis—the idea that Alzheimer’s can be caused by infectious microbes like bacteria and viruses.
A dedicated group of scientists from around the globe have studied and published on the topic of microbes and Alzheimer’s for the last three decades. Evidence has zeroed in on a handful of bacteria and viruses that may have the ability to cause Alzheimer’s in certain patients, but a definitive relationship remains elusive due to scientific, behavioral and economic reasons. Enter COVID-19.
Learning from a New Germ
Over the last 20 months, our world has been rocked by the emergence of a novel respiratory virus. Beyond the immediate threat COVID-19 poses to humans, doctors and researchers are closely monitoring and studying lingering chronic effects. A major area of concern is the long-term impact that the COVID-19 virus has on the brain as a recent study of COVID-19 survivors revealed 60 percent of 400 patients experience lasting cognitive impairment, with one in three experiencing significant “dementia-like” symptoms.
For the researchers that have advocated for the infection hypothesis of Alzheimer’s, this isn’t surprising. It is another pathogen that can affect the brain, adding to a list of other better-characterized viruses, bacteria, parasites and fungi. In fact, this pandemic has the potential to help us better understand the relationship between other microbes and Alzheimer’s by unveiling new germ-human interactions, testing methods, and importantly — a serious influx of funding as the National Institutes of Health has pledged $1 Billion to study “long COVID”.
Since the COVID-19 virus isn’t really being found inside brain tissues of deceased patients, it appears to induce brain inflammation and neurologic damage without necessarily being at the scene of the crime. It may be that this virus induces such a powerful inflammatory response that it causes permanent damage, similar to the lasting impact seen in football players with repeated head trauma. It seems relatively intuitive that a germ could cause damage to the brain, but is it too simple of an explanation?
The C-word (Cause)
Some say that it is too easy for an infection to be the cause of such a complex disease, but that statement is in direct contrast with significant historical examples. The Human Papilloma Virus (HPV) causes cervical cancer. A gut bacterium called H. pylori causes stomach ulcers, gastritis, and is now implicated in certain gastrointestinal (GI) cancers. Yes, Alzheimer’s is complex, like cancer, but this “germ theory” is both evolutionarily plausible and calls attention to the intricate relationship that we have with our “passengers,” our microbiome. Certain pathogens can readily enter the human central nervous system (CNS), become chronic and generate inflammation. Let’s look at some of the evidence preceding COVID-19’s arrival.
Why Do Amyloid “plaques” Show up?
Dr.’s Rudolph Tanzi and Robert Moir at Harvard added an important piece to this puzzle by demonstrating that the presumed offender, beta-amyloid, possesses significant anti-infective properties. Given the lack of clinical benefit to patients with anti-amyloid drugs like the recently-approved Biogen drug, Aduhelm, there is an urgent need to look upstream and pivot toward diverse approaches that do not target pathology but rather the underlying root cause(s). In other words, what is beta-amyloid and why is it there in the first place?
Alzheimer’s Isn’t All the Same
Most experts agree (and the data concurs) that Alzheimer’s is not a homogenous disease, and that the drivers and vulnerability likely vary from one person to the next. For example, environmental pollution, toxins, lifestyle, genetics, the microbiome and infectious diseases all appear to be important. With that, funding needs to flow toward a diverse array of concepts that address early events with the potential to drive the pathology.
Gathering the Clues
To better understand this relationship between microbes and Alzheimer’s, researchers have infected mice with “suspect” pathogens, and observed Alzheimer’s-like pathology. In one study, conducted by Dr. Brian Balin at the Center for Chronic Disorders of Aging at the Philadelphia College of Osteopathic Medicine, they gave a common respiratory form of Chlamydia called C. pneumoniae to mice through their noses. The mice developed amyloid plaques, and Dr. Balin’s team also noted that antibiotic therapy given promptly following the nasal infection stopped the spread of amyloid plaques in the mice.
In spite of compelling evidence implicating germs, only a few human antibiotic or antiviral therapy studies have been prospectively conducted or retrospectively reviewed in Alzheimer’s. A major flaw of all of the previous and ongoing studies is the lack of comprehensive microbe detection that would pick up many possible offenders. If a person has a brain infection involving more than one germ, Herpes Simplex Virus and C. pneumoniae for example, giving an antiviral or antibiotic alone may not yield meaningful results for that patient because they may have what is called a “polymicrobial infection.” There is a type of testing called Next-Generation Sequencing that could help identify a thousand or more pathogens with one blood or spinal fluid test by detecting and measuring the quantity of microbe’s DNA. This would allow for precise treatment in patients with documented central nervous system infections.
A Difficult Organ to Study
Studying the brain of a living person is a significant fundamental barrier to Alzheimer’s research, but “germ theory” researchers have studied post-mortem Alzheimer’s brain tissues as well as those of non-Alzheimer’s, age-matched individuals. These studies reveal significantly larger numbers of common germs such as Herpes Viruses, Chlamydia pneumoniae, periodontal bacteria like Porphyromonas gingivalis, and tick-borne infections like the one that causes Lyme Disease (Borrelia burgdorferi) among others. Many of these microbes can cause acute brain infections resulting in meningitis or encephalitis, they can also become chronic hiding from the immune system inside our cells. Given their behaviors and their acute consequences in certain patients, it’s not outlandish to investigate their role in chronic brain diseases like Alzheimer’s. All of this said, why aren’t we spending more research and development (R&D) dollars on identifying and treating this possible subset of infection-driven Alzheimer’s patients?
Dogma and Resistance to New Ideas
In part, human behavior helps answer that question. Historically, big shifts in thinking come with a healthy dose of denial and discomfort in medicine. The “gastric ulcer — Helicobacter pylori bacteria” example is not only a scientific parallel to the germ theory of Alzheimer’s, but it is also a perfect illustration of the scientific communities’ reaction to new ideas. In spite of a decade of credible research, beginning in 1982, demonstrating that this sneaky bacterium, H. Pylori was present alongside gastric ulcers, the GI community fervently refused the idea that the bacterium caused the ulcer.
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At the time, it was believed that lifestyle, stress, diet and smoking were the culprits to blame for this condition. Medications to reduce acid were prescribed, masking the root cause of the ulcers. In presenting this hypothesis and their thorough research, Dr.’s Barry Marshall and Robin Warren met scathing criticism. In fact, Dr. William Hughes wrote an entire book dedicated to documenting this controversy entitled “The Great Ulcer War.” It was indeed a war.
In a brazen and unprecedented maneuver, Dr. Marshall swallowed a broth containing the bacteria. He fell ill and underwent a biopsy to prove his theory. Not only were Marshall and Warren proven correct, they eventually saved millions of lives by elucidating a cure for the root cause of the dangerous bleeding ulcers — cheap generic antibiotics. They won the Nobel Prize in 2005.
History reveals this pattern of human behavior at the threshold of many great innovations. Arthur Schopenhauer’s words sum it up nicely: “All truth passes through three stages. First, it is ridiculed. Second, it is violently opposed. Third, it is accepted as being self-evident.” In short, we must learn from history by questioning our assumptions and pressure-testing old ideas, even if it makes us uncomfortable.
Follow the Money
As in the case of H. pylori and the ulcers, there is a third and truly critical component to the Alzheimer’s landscape; economics. At the time when Marshall and Warren were working to expose this germ to the GI community, profitable branded acid-reducing drugs were dominating the treatment and R&D scene. Some felt that the relationship between industry and key scientists and physicians fueled a lack of enthusiasm for H. pylori research, which, would in many cases negate the need for a lifetime of profitable drugs.
In the infectious Alzheimer’s space, there are economic drivers with the ability to impact investment strategies and research dollars. The global anti-infective drug space has been struggling for over a decade even though these life-saving medicines are needed to address drug-resistant infections that afflict 2.8 million people per year in the United States alone. While utterly important for our survival, antimicrobials are generally prescribed for seven to 10 days and only yield a meager fraction of the price of other types of treatments, like oncology drugs. Once a new anti-infective drug is to market, physicians “reserve” the new ones for a time when the cheap generic ones no longer work. So, there is a per-pill and treatment duration profitability issue topped off by a lack of demand.
The market prior to COVID-19 reacted by investing in more profitable spaces, like rare diseases. While the pre-2021 antimicrobial space has likely dampened an appetite for anti-infective Alzheimer’s strategies, there is good news. It’s actually this awful pandemic, COVID-19.
The Silver Lining
Because of COVID-19 our world has come to appreciate the importance of infection research both in the acute and chronic setting, new and scalable pathogen testing methods are being developed that can be reimagined for other germs. Novel anti-viral treatments and vaccine platforms are in development that may be repurposed to support the prevention and treatment of other deleterious microbes, such as the ones associated with Alzheimer’s.
As a result of the use of antibiotics for supportive care in COVID-19 patients, many are concerned that antibiotic resistance is surging. This has heightened the need for novel antimicrobials. Recently, big companies like Pfizer, have announced they are once again backing anti-infectives.
All of this sets the stage for germ-theory researchers and innovators to explore this possible subset of Alzheimer’s patients. Where these two pandemics converge, Alzheimer’s and COVID-19, we have a chance to clarify an old hypothesis that deserves to get a fresh look as much as Alzheimer’s patients and their families deserve precise, effective treatments.
On the heels of her own serious illness, Nikki Schultek founded Intracell Research Group, a mission-driven global medical research consortium clarifying the role of microbes in Alzheimer’s and other chronic diseases. She is connecting physicians, researchers, and industry, building research collaborations and advising companies innovating in this space, and publishing alongside global experts.