For decades the neuroscience community has focused almost exclusively on beta-amyloid in the brain as the primary cause of Alzheimer’s disease [AD]. Billions have been spent developing dozens of drugs designed to rid the brain of beta-amyloid plaques. We have written about the controversy surrounding the FDA approval of aducanumab (Aduhelm). You can find that article (“Breakthrough or Boondoggle”) at this link. The beta-amyloid theory of dementia is losing momentum, though. New research from Sweden suggests that infection is contributing to Alzheimer’s disease (Journal of Alzheimer’s Disease, Feb. 2, 2024).
The Slowly Sinking Amyloid Theory:
Scientists hate to give up their pet theories. Perhaps that is why the beta-amyloid approach to Alzheimer’s disease has persisted for so long. There are still a great many researchers who are clinging to this sinking ship despite the preponderance of evidence questioning it.
Research was published in JAMA Neurology (Sept. 19, 2022) that put a chink in the amyloid armor. Two studies of the drug crenezumab lowered beta-amyloid in the brain “…but did not reduce clinical decline in participants with early AD [Alzheimer disease].”
You can read our review of that research and get an overview to the question: amyloid or infection is contributing to Alzheimer’s Disease? at this link.
Why Are There No Effective Alzheimer’s Drugs?
New studies challenge the amyloid theory of Alzheimer’s disease. Is that why there are no effective Alzheimer’s drugs? Another drug fails!
Through the Looking Glass:
Noam Chomsky is a renowned scholar of linguistics and philosophy. He observed that:
“Science is a bit like the joke about the drunk who is looking under a lamppost for a key that he has lost on the other side of the street, because that’s where the light is. It has no other choice.”
When it comes to Alzheimer disease (AD), this metaphor seems sadly appropriate. Dr. Alois Alzheimer was a neuropathologist who first identified the disease that carries his name at the turn of the 20th century. He described the plaques and tangles that pathologists still rely upon to diagnose this dementia.
A rival scientist, Dr. Oskar Fischer, described similar patients around the same time. He hypothesized that the distinctive plaques of AD might have resulted from brain infection. This possibility was overlooked for nearly a century.
Looking Under the Wrong Streetlight?
An extraordinary amount of money has been spent trying to develop medications that would reduce amyloid plaque. These clumps of sticky protein are characteristic of Alzheimer disease. Drug companies have been incredibly successful at creating expensive monoclonal antibodies that have been very good at removing amyloid plaque from the brain. The assumption has been that getting rid of the plaque would reverse the course of dementia.
After dozens of drug failures, it seems that perhaps drug companies have been looking under the wrong streetlight. Although the FDA has approved two monoclonal antibodies that are very effective at removing amyloid plaque from the brain, these drugs do not reverse dementia.
“Bugs” in the Brain?
Neuroscientists have considered amyloid beta, the primary component of plaque, as the brain’s enemy. But they have not asked a more fundamental question: what is it doing in the brain? Some scientists speculate that it is part of the brain’s immune response to infections. Should researchers have been asking if infection is contributing to Alzheimer’s disease?
Over the last few decades, scientists have discovered the importance of the microbiome. Initially they focused on the bacteria, fungi and viruses in the digestive tract. More recently, though, they have realized that there is a microbiome in the lungs, on the skin and even in the brain.
The idea that viruses might be contributing to dementia is not yet mainstream, even though researchers have found evidence of a link for 50 years. In 1974, scientists noted that people with dementia were more likely to have antibodies to the herpes simplex virus (HSV) responsible for cold sores (British Journal of Psychiatry, March 1974). Pathologist Melvyn J. Ball made an explicit hypothesis connecting HSV to lesions in the brain in 1982 (Canadian Journal of Neurological Sciences, Aug. 1982).
Swedish Scientists Have Been Asking if Infection Is Contributing to Alzheimer’s Disease:
We love Swedish scientists. They are seemingly a more curious and independent lot. Recent research from Sweden supports Dr. Ball’s hypothesis. Scientists there have found that people with evidence of HSV infection were twice as likely to develop dementia during a 15-year study (Journal of Alzheimer’s Disease, Feb. 2, 2024).
Not the First Swedish Study Showing Infection Is Contributing to Alzheimer’s Disease:
A nationwide study of health records in Sweden (PLoS One, Sept. 15, 2022) suggests a connection between serious infection and early diagnosis of Alzheimer disease. The scientists were not looking at COVID-19 infections. They were focusing on infectious diseases in general. In particular, they studied infections requiring hospital treatment.
The investigators reviewed records of more than 12 million Swedish adults between 1970 and 2016. Those with a history of hospitalization for infections in early and mid-life were 16 percent more likely to earn a diagnosis of Alzheimer disease before age 60. Infections were also linked to a very modest increase in the risk of Parkinson disease [PD], by about 4 percent.
Somewhat surprisingly, both bacterial and viral infections showed an association with these two neurodegenerative diseases. Several different sites of infection, including the urinary and digestive tracts, were implicated.
The authors conclude:
“In conclusion, our study suggested that individuals with hospital-treated infections, especially in those occurring in early- and mid-life, had an increased risk of developing AD and PD, attributable to cases diagnosed before 60 years. Further studies are warranted to validate these findings, to elucidate underlying mechanisms, and to determine whether better control of hospital-treated infections could prevent or delay onset of neurodegenerative diseases, especially the ones with an onset relatively early in life.”
Proving Cause and Effect Is Hard!
As we have learned from the beta-amyloid theory of Alzheimer’s disease, establishing a mechanism behind a disease is difficult. The kind of observational study carried out by the Swedish researchers cannot establish a cause-and-effect relationship. It does, however, suggest that infection is contributing to Alzheimer’s. How that is happening remains to be determined.
The authors point out, though, that:
“The association between infections and an increased risk of AD has support from previous studies.”
They go on to note that:
“These findings suggest that infectious events may be a trigger or amplifier of a preexisting disease process, leading to clinical onset of neurodegenerative disease at a relatively early age.”
The FDA, Drug Companies and Amyloid:
Pharmaceutical companies and the Food and Drug Administration have been all in on amyloid for a long time. But removing amyloid plaque has not worked well and can cause serious side effects.
Instead, some scientists are calling for research to determine if vaccinations against herpes viruses might protect the brain. Others are interested in well-controlled large trials of inexpensive antiviral medications such as acyclovir or valacyclovir. Preliminary studies suggest that such anti-herpes drugs might be helpful, with few adverse reactions (Alzheimer’s & Dementia, June 9, 2021).
To learn more about the possible connection between herpes infections and Alzheimer’s disease, here is a link you may find interesting.
You will learn about Dr. Melvyn Ball. This pathologist proposed viral infection as a contributor to Alzheimer’s disease 40 years ago. In particular, Dr. Ball was interested in herpes viruses. Sadly, his research was ignored for decades.
More modern research comes from Harvard. We had the honor to interview Dr. Robert Moir, a truly innovative thinker. You can listen to our podcast with Dr. Moir and neuroscientist Dr. Dale Bredesen at this link:
Show 1132: Are Infections to Blame for Alzheimer Disease? (Archive)
Pharmaceutical scientists have been striving to get amyloid plaques out of the brain, but new research suggests that amyloid may be acting to protect the brain from microbes. What are the implications
Why Should We Care?
The pharmaceutical industry has missed the boat when it comes to developing effective new treatments for Alzheimer’s disease. This devastating illness causes untold misery for millions of families.
It is time for researchers to break out of the beta-amyloid mold and start exploring new causes and treatments for AD. Otherwise, we will be overwhelmed by an epidemic of dementia in the years ahead. We wish that funding agencies like the NIH and the Alzheimer’s Association would support this kind of research. Perhaps it’s time for neuroscientists to stop looking under the amyloid beta streetlight and seek the underlying cause of amyloid accumulation.
To learn more about the connection between COVID and AD, check out this article. And if you are curious about how vaccines might protect against dementia, here is a recent post.
