For decades researchers have told us that beta amyloid accumulation in the brain causes Alzheimer disease (AD). The FDA has recently approved two new drugs, Aduhelm and Leqembi, based on this theory. There is a third drug, donanemab, waiting on the runway. All three medications are very good at removing amyloid plaque from the brain, but do they do anything meaningful to improve the clinical outcome of patients with Alzheimer disease? Perhaps it is time to think different…to quote an old Apple computer commercial.
Beta Amyloid and Alzheimer Disease:
What, you may wonder, is beta amyloid and why does it accumulate in the brain? Previous scientists have found that amyloid precursor protein (APP) becomes beta amyloid when pathogens attack the brain.
However, researchers have reacted in quite different ways to that information. Some have suggested that we should be looking at brain infections and ways to protect against them. The dominant approach, though, has been to try to get beta amyloid out of the brain.
Why Should We Think Different About Alzheimer Disease?
The 90+ Study was started in 2003. It enrolled over 2,000 volunteers. The goals of the research include:
- “Determine factors associated with longevity: What makes people live to age 90 and beyond? What types of food, activities or lifestyles are associated with living longer?
- Examine rates of cognitive and functional decline in the oldest-old: How do memory loss and disability affect those in their 90s? How can people prevent memory loss and disability at this age?”
Neuroscience News (May 24, 2023) reports the latest discovery from the 90+ Study (Journal of Alzheimer’s Disease, (May 16, 2023):
“Summary: A new study found people who are 90+ and have superior cognitive skills have similar levels of brain pathology as Alzheimer’s patients.
The study included 102 cognitively normal individuals who died at a mean age of 97.6 years.
The researchers used autopsy data and cognitive test scores to assess the participants’ brain health and cognitive function.
People who are 90+ and have superior cognitive skills have similar levels of brain pathology as Alzheimer’s patients.”
The authors of the research state:
“Our findings indicate that Alzheimer’s Disease pathology and vascular changes are common in the brains of 90+ people with excellent cognitive abilities, meaning they are resilient to such changes.”
Why Should Such a Finding Make Us Think Different?
If people in their late 90s have ugly looking brains upon autopsy but still have good cognitive ability up until the time of their deaths, we really need to rethink some of our basic beliefs about what causes AD. Perhaps amyloid is not the enemy we have always assumed.
On our nationally syndicated radio show, we consider the causes of Alzheimer disease. For decades, one theory has dominated. It suggests that the accumulation of beta-amyloid plaques found in the brains of people with dementia cause the problem. Is it time to think different about Alzheimer disease?
How to Think Different About Alzheimer Disease:
Our guest is a medicinal chemist as well as a respected neurologist. He and his team are working on developing medications that could help people prevent or overcome Alzheimer disease. His biggest contribution is finding a way to think different about Alzheimer disease and beta amyloid.
With all the evidence that has accumulated, it doesn’t make sense to dismiss beta amyloid as unimportant. On the other hand, research efforts concentrated solely on beta amyloid have not yielded treatments that are clearly safe and effective enough for most people. Instead, Dr. Donald Weaver suggests that we should look at this compound as a desperate attempt by the brain in the throes of an autoimmune disease.
Autoimmunity and the Brain:
So far, we have only a hypothesis that Alzheimer disease is the result of the body attacking the brain. However, many of the factors that can contribute to dementia are the sorts of insults that can kickstart an immune response. These include things like air pollutions, infection (such as with herpes virus) and head trauma from sports, accidents or domestic violence.
Dr. Weaver draws a distinction between autoimmunity related to the adaptive immune system and that linked to the innate immune system. We have many examples of the former, such as rheumatoid arthritis or systemic lupus erythematosus (SLE). We don’t yet have other examples of the innate immune system attacking to cause autoimmune conditions. We’ll be watching for more research.
Fighting Autoimmune Disease in the Brain:
Dr. Weaver and his lab hope that their research will lead to diagnostic approaches as well as therapeutics. He has been investigating the metabolism of tryptophan in the brain as a precursor of dementia and beta amyloid (Alzheimer’s & Dementia, April 6, 2022). If this approach as a way to think different about Alzheimer disease pans out, it could lead to blood tests many years before cognitive symptoms appear. In addition, scientists may be able to develop drugs that can calm the cytokine storm in the brain that appears to trigger the damage (Alzheimer’s & Dementia, Sep. 27, 2022).
Donald Weaver, MD, PhD, is both a medicinal chemist and clinical neurologist, focused on the design and development of new therapies for Alzheimer disease and related dementias. Dr. Weaver is Senior Scientist at the Krembil Brain Institute at the University Health Network, Toronto, Canada. He is a professor of Medicine (Neurology), Chemistry, and Pharmaceutical Sciences at the University of Toronto and a neurologist at the Toronto Western Hospital. Dr. Weaver is also Chief Medical Officer of Treventis Corporation and is the former President of Epilepsy Canada. His website is https://www.weaverlab.ca/drweaver/
Listen to the Podcast:
The podcast of this program will be available Monday, Jan. 16, 2023, after broadcast on Jan. 14. You can stream the show from this site and download the podcast for free.
Here is a link to our interview with Dr. Matthew Schrag of Vanderbilt University. He has also forced us to think different about the dogma of Azheimer Disease. We think you will find this radio show worth your time! His work also challenges the paradigm that beta amyloid is the key factor behind AD.