Although the main cause of Alzheimer’s disease is still under debate, many researchers believe the buildup of
Now, a team of researchers from Yale University discovered evidence suggesting the swelling caused by amyloid plaques in the brain may be the true cause of Alzheimer’s disease. They conducted their study in a mouse model.
Additionally, the team identified a biomarker to help doctors better diagnose the disease and provide a future therapeutic target.
The study was recently published in the journal
Previous research has shown that amyloid plaques can occur
Using a mouse model, researchers found that each amyloid plaque in the brain causes swelling along any nearby
Additionally, the formation of groups of
According to researchers, as the swelling on the axons increases, information is no longer able to move from one area of the brain to another, likely triggering dementia.
“Our study shows that the enlargement of the swellings is critical for causing electrical conduction blockages in axons,” Dr. Jaime Grutzendler, the Dr. Harry M. Zimmerman and Dr. Nicholas and Viola Spinelli professor of neurology and neuroscience at the Yale School of Medicine and senior author of the study, told Medical News Today.
“Swellings in axons act as a capacitor — similar to electrical circuits — that acts as an electric current sink. This prevents the normal transmission of electrical signals through the axons, thereby disrupting communication with hundreds of other neurons.”
“Since each amyloid plaque is surrounded by hundreds of axons with swellings and each axon is connected to hundreds of other neurons and given that there are millions of amyloid plaques in the brain in Alzheimer’s, you can do the math and realize that there is a potential to disrupt billions of connections in the brain by these swelling mechanism,” Dr. Grutzendler added.
In the present study, the researchers also identified a potential new
During the study, researchers used
“We identified a molecule in lysosomes that when accumulated in excess makes these swellings get bigger,” Dr. Grutzendler told MNT.
“Importantly, when you reduce PLD3 with gene therapy the swellings are reduced and this leads to improvement of electrical conduction in axons as well as improvement in the communication between different neurons connected through those axons,” he noted.
The research team believes doctors can potentially use PLD3 as a biomarker to help diagnose Alzheimer’s risk, as well as provide a target for future therapies.
When asked about the next steps for this research, Dr. Grutzendler said they would be to continue doing rigorous studies to better understand how swellings form in the very beginning as soon as a tiny deposit of amyloid accumulates.
“Also important to understand how swellings affect electrical conduction,” he added. “More importantly, we will continue our studies [to understand] the various molecules that are involved in the initial formation and growth of wellings with the goal of finding therapeutic targets that could eventually be translated to humans.”
MNT also spoke with Dr. Jennifer Bramen, a senior research scientist at the Pacific Neuroscience Institute at Providence Saint John’s Health Center in Santa Monica, CA, who was not involved in this study.
She said that while
“One of the features of Alzheimer’s disease is impaired connections between brain regions,” Dr. Bramen explained. “Amyloid plaques are a hallmark of Alzheimer’s disease.”
“The authors describe one way that amyloid plaques might cause this disruption in electrical signals between brain regions. This is through the axonal swellings, which interrupt the flow of electricity in mice in their experiments.”
“As a researcher, I would like to see more work reproducing and building on these findings,” she added. “Most importantly, I would like to see research to support these findings in humans.”
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Alzheimer's: Swelling on axons may be the true cause – Medical News Today