Rediscovering the causes of Alzheimer’s disease
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’s 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.
For the last several decades, drug companies have spent billions of dollars trying to develop medications that would reduce amyloid plaque. These clumps of sticky protein are characteristic of Alzheimer’s disease. The assumption has been that getting rid of the plaque would reverse the course of the disease.
But after dozens of drug failures, it seems that perhaps drug companies have been looking under the wrong streetlight. Although the Food and Drug Administration recently approved two new monoclonal antibodies that are very effective at removing amyloid plaque from the brain, these drugs don’t reverse dementia.
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.
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, August 1982).
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 15year study (Journal of Alzheimer’s Disease, Feb. 2, 2024).
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).
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.
In their column, Joe and Teresa Graedon answer letters from readers. Write to them in care of King Features, 628 Virginia Drive, Orlando, FL 32803, or email them via their website: www.PeoplesPharmacy.com. Their newest book is “Top Screwups Doctors Make and How to Avoid Them.”