Breakthroughs in Alzheimer’s research may be game-changers
Even as new drugs come to market, further study appears to point to infections as a possible cause for the debilitating disease that affects more than 7 million people in the U.S. alone.
Research on Alzheimer’s disease is approaching a much-needed tipping point. The media spotlight has been on newly available drugs like lecanemab and donanemab that target the protein plaques associated with the disease’s progression. But a burgeoning consensus is emerging around a longstanding hypothesis that was once considered unorthodox and quixotic: Infections may trigger or exacerbate Alzheimer’s disease and other neurological conditions.
It’s a straightforward hypothesis with profound implications for how we diagnose and treat a debilitating disease that impacts nearly 7 million Americans (and about 55 million people worldwide). Health-care and caregiving costs associated with Alzheimer’s disease are believed to exceed $600 billion annually.
A hallmark of Alzheimer’s disease, the most common form of dementia globally, is chronic brain inflammation. For decades, Alzheimer’s disease researchers have searched for a missing puzzle piece: What drives this inflammation?
Now, spurred by the prolonged neurological symptoms that many people experienced after COVID-19 infections, such as brain fog and loss of their sense of smell, scientists are more focused on infection as an underlying driver of inflammation across the human body.
Numerous bacteria, viruses, fungi, and parasites are capable of entering the brain. One example is the bacterium that causes Lyme disease. Another is an airborne bacterium, Chlamydia pneumoniae, that was first found in Alzheimer’s-diseased brains by Dr. Balin and colleagues as far back as 1998. Other microbes, such as those residing in the gut or the mouth, may impact and inflame the brain by triggering body-wide inflammatory responses.
The fact that some bacteria appear to protect some people against this inflammation only reinforces the complex and important relationship between humans and our many invisible passengers.
This extends beyond dementia and Alzheimer’s disease. Several neurological conditions, including multiple sclerosis, have been linked with infections or changes in the collection of microbes inside all of us, but establishing a causal relationship has remained elusive.
Even so, there are case reports in medical journals of “reversible dementias” caused by infections. In these reports, doctors identified underlying infections, and patients improved drastically once they received targeted treatments.
Knowing all this, why aren’t we more focused on testing and treatments for potential infectious drivers of inflammatory diseases? There are three key reasons.
- Medical paradigm shifts are notoriously slow. Rather than targeting potential root causes of Alzheimer’s disease, drug developers have largely worked to reduce the disease’s progression, such as by targeting the plaques of the protein amyloid that can show up in the brain. Another example of this phenomenon was the rise of profitable drugs for stomach ulcers that didn’t treat the root cause. (It was later discovered that a bacterium, Helicobacter pylori, was causing the ulcers.)
- Drugs that fight infection are among the least profitable for the drug industry. This reduces investors’ appetite for funding preventive approaches to treating (or potentially curing) diseases associated with chronic infection, despite the growing need for such options.
- The science is complicated. It’s hard to demonstrate that a microbe or infection causes a disease. Microbes can be stealthy, testing tools are imperfect, and responses to a single infection can vary greatly from person to person — as we know well from collective experience with COVID-19. Also, chronic diseases unfold over many years and involve multiple variables, making them difficult to study.
Still, there is cause for hope.
Earlier this year, before the Alzheimer’s Association International Conference in Philadelphia, a group of scientists gathered a few miles away at Philadelphia College of Osteopathic Medicine (PCOM) as part of the Alzheimer’s Pathobiome Initiative. Joining scientists at PCOM were colleagues from Baylor, Columbia, Drexel, Harvard and Massachusetts General Hospital, The Hebrew University in Jerusalem, Oxford, Pittsburgh, and Tulane, among others — all sharing findings that point to the significance of the so-called “infection hypothesis” in Alzheimer’s disease and other neurological diseases.
Recently, our research group highlighted how infection can interfere with senses such as vision, hearing, and smell, causing them to malfunction in a possible early warning sign of Alzheimer’s disease.
The growth of this scientific community, and its collaborative spirit, reflect the level of compelling evidence already accumulated, as well as the urgency of the cause. Global cases of dementia are expected to nearly double every 20 years, each case taking a profound toll on the patient and their loved ones.
We’re at the edge of a breakthrough in understanding conditions ranging from Parkinson’s disease to mental illness. After decades without effective treatments, people are listening, and scientists are taking action.
Nikki Schultek is executive director of the Alzheimer Pathobiome Initiative (AlzPI) and founder of Intracell Research Group. In remission from chronic infection, she worked in the pharmaceutical industry before focusing on interdisciplinary research and advocacy.
Brian J. Balin, PhD, is professor of neuroscience and neuropathology and director of the center for chronic disorders of aging at Philadelphia College of Osteopathic Medicine (PCOM). He is internationally recognized in the field of Alzheimer’s disease research and is a founding member of the Alzheimer’s Pathobiome Initiative (AlzPI).