THE SEARCH FOR A CURE FOR ALZHEIMER’S DISEASE has recently become increasingly contentious. Are we way off the mark on this form of dementia? What, you may ask, Alzheimer’s may not be a brain disease?
Today, we will explore the dominant Alzheimer’s hypothesis: a brain protein subtype (beta-amyloid) causes Alzheimer’s disease. We will also look at an alternative theory.
The story veered off course when in 2022, Science magazine reported that a celebrated 2006 research paper published in Nature, which named beta-amyloid as the cause of Alzheimer’s, might have been based on fabricated data.
What if, instead of thinking of Alzheimer’s as a brain disease, we reframe the story as the brain’s immune system goes awry?
“Memories warm you up from the inside. But they also tear you apart.”
― Haruki Murakami, Kafka on the Shore
Beta-amyloid, under the microscope
The toll Alzheimer’s disease takes on brain tissue is evident under a microscope. While scientists don’t fully understand what causes brain cell death and tissue loss, tangles and plaques in the brain are leading suspects.
I want to dig deeper into the amyloid theory, as it is relevant to our story today.
- Plaques form when protein pieces (beta-amyloid (BAY-tuh AM-uh-loyd)) clump together. Beta-amyloid comes from a larger protein in the fatty membrane surrounding nerve cells.
- Beta-amyloid is “sticky” and gradually builds up into plaques. A few pieces of beta-amyloid forming a group may be particularly problematic. These small collections can interfere with cell-to-cell signaling between nerve cells.
- Beta-amyloid clumps can also activate immune system cells, triggering inflammation and devouring disabled cells. Finally, tangles destroy an essential cell transport system composed of proteins.
- In normal brains, parallel strands deliver key materials to the cells. The protein tau helps to keep these strands straight. In damaged brains, tau collapses into strands known as tangles. The strands can no longer remain straight and disintegrate. In brain areas with tangles, nutrients and other essential supplies cannot move through the cells, leading to cell death.
Beta-amyloid, a history
In 1892, Paul Blocq and Georges Marinesco at the Salpêtrière Hospital in Paris (France) reported microscopic “amas ronds” (round clusters, or round heaps) or “nodules de sclérose névroglique” (nodules of neuroglial sclerosis) in the brains of older patients having seizures.
Six years later, Emil Redlich published evidence linking plaques to dementia in three elderly patients.
Redlich described the plaques as having a core or uncertain material and surrounding astrocytes (nerve cells) and their processes. Given the plaques looked like millet seeds, he called the overall lesion “miliary sclerosis.” Redlich also called the lesions plaques, a term subsequently expanded to “senile plaques” by Simchowicz in 1911.
In addition, Redlich reported that some small lesions consisted of fine fibers with a cotton-like appearance, foreshadowing the subsequent description of “cotton-wool plaques” to describe certain deposits today.
Although Alois Alzheimer is often credited with instigating the burst of scientific analyses of plaques with his 1906 conference presentation in Tübingen (published in 1907) [95], his report was brief, and plaques (‘miliary foci’) were only superficially mentioned2. He did not issue his first detailed histopathologic examination of plaques until 1911 [96].
In 1892, Paul Blocq and Gheorghe Marinescu first described the presence of plaques in grey matter. They called these plaques “nodules of neuroglial sclerosis.” In 1898, Emil Redlich reported plaques in the brains of three patients, two of whom had a diagnosis of dementia.
Beta-amyloid theory dominates
For many years, scientists have attempted to create novel treatments for Alzheimer’s disease by preventing the formation of brain-damaging clumps of the mysterious protein beta-amyloid.
Donald Weaver recently got my attention we he offered this observation in Science Alert:
Scientists have arguably got ourselves into an intellectual rut [emphasis added], concentrating almost exclusively on this approach, often neglecting or ignoring other possible explanations.
As noted above, Science magazine reported in 2022 that a critical 2006 Nature research study — which identified a beta-amyloid subtype as Alzheimer’s cause — may have been based on fabricated data.
This narrow focus on abnormal protein clumps has not yielded a useful drug or therapy.
Admittedly, in 2021, the US Food and Drug Administration approved aducanumab, an antibody-targeting beta-amyloid for Alzheimer’s treatment. However, the data supporting its use were incomplete and contradictory.
A new theory of Alzheimer’s disease
Weaver’s lab at the Krembil Brain Institute (Toronto, Canada) is offering a new “out-of-the-clump” way of thinking about Alzheimer’s. Listen to him describe a novel view:
“Based on three decades of research, we no longer think of Alzheimer’s as primarily a brain disease. Rather, Alzheimer’s is principally a disorder of the brain’s immune system.”
The immune system, present in every organ, is made of molecules and cells that work harmoniously to help repair injuries and protect the body from foreign invaders.
Got an infection? Enter the immune system to fight the microbial invades. Trip and fall? Here comes the immune system to help repair damaged tissues.
When we trip and fall, the immune system helps to fix the damaged tissues. When there is a bacterial or viral infection, the immune system helps to fight these microbial invaders.
Alzheimer’s may be an immune system condition.
The brain has an immune system, too. If an infection enters the brain, the immune system arrives to battle. With trauma, the immune system arrives.
To Weaver, beta-amyloid is a normally occurring molecule that is part of the brain’s immune system. The molecule contributes to the brain’s overall immune response.
Sometimes, things go awry: Beta-amyloid cannot easily distinguish fat molecules composing bacteria membranes versus ones making up brain cell membranes. Beta-amyloid mistakenly attacks the brain cells it is supposed to protect. We may think of Alzheimer’s as an autoimmune disease.
Unfortunately, the steroids that can help other autoimmune diseases (such as rheumatoid arthritis) do not work against Alzheimer’s. The brain is the most complex structure in the Universe.
I hope this novel theory of Alzheimer’s disease will lead to the development of effective drugs for the disease. Alzheimer’s may not be a brain disease but an autoimmune one. I will end with five simple ways to drop your dementia risk:
5 Simple Ways to Drop Your Dementia Risk
WHILE THERE IS NO CURE FOR ALZHEIMER’S DISEASE, there are some lifestyle moves you can make that may lower your risk of…medium.com
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The information I provided in this blog is for educational purposes only and does not substitute for professional medical advice. Please consult a medical professional or healthcare provider for medical advice, diagnoses, or treatment. I am not liable for risks or issues associated with using or acting upon the information in this blog.
Thank you for reading “Are We Off the Mark on Alzheimer’s? It Might Not Be A Brain Disease.”
