Yale’s School of Medicine is bringing an innovative Alzheimer’s treatment in focus, detailing their approach in a recent study. The approval of the amyloid-targeting drugs Kisunla and Leqembi have been exciting new developments for the 7 million people living with Alzheimer’s Disease in the U.S., as well as their caregivers. While these treatments began a new era in Alzheimer’s research, there are still more avenues to go down.

The new study by Yale scientists suggests targeting axonal spheroids—a byproduct of amyloid plaques—may open up new treatment options. Targeting them could provide a renewed sense of hope for the millions who suffer with this debilitating disease.

What Are Axonal Spheroids?

The human brain is made up of 100 billion neurons—or nerve cells—that send messages to the rest of the body through pathways of electrical impulses. Neurons help our bodies function, telling us how to breathe, talk, eat, walk, and think.

Axons—part of the neuron—send these messages. Damaged axons form bubble-like structures known as axonal spheroids. These structures are frequently observed surrounding amyloid plaques—abnormal clumps of a protein called beta-amyloid. These clumps accumulate in the brain of someone with Alzheimer’s disease and are known to contribute to axonal damage.

Amyloid plaques disrupt the internal functions of nearby neurons. This leads to the accumulation of lysosomes, cellular organs responsible for removing cellular waste from the cell. When lysosomes begin to accumulate, their jobs are disrupted and waste builds up in the neuron. This impedes the transmission of electrical signals, contributing to the neurological deficits observed in Alzheimer’s.

Focusing on Axonal Spheroids

The aim of the Yale study was to determine what axonal spheroids are, how they form, and how this information could be used as targets to restrict their growth.

“Our research introduces a new hypothesis that axonal spheroids are a potentially very important pathological process,” Jaime Grutzendler, MD, lead author of the study stated in this article, “We believe targeting these spheroids could be an important future avenue for treating Alzheimer’s disease by improving the overall electrical conduction and brain circuits—rather than just simply removing the amyloid plaques.”

What Did the Study Find?

Using both mouse and human brain tissues, researchers introduced antibodies that bind to a specific protein in axonal spheroids. The protein was then used as a central place from which they tagged all the other proteins surrounding it. Within the spheroids, they discovered hundreds of previously unknown proteins.

Researchers also identified several signaling pathways. These pathways are a sequence of chemical reactions allowing cells to communicate and carry out their major functions. And one of those pathways was found to be overactive in the spheroids.

They then applied amyloid to neurons, which caused them to develop structures similar to axonal spheroids. When they introduced a drug that blocked the pathway, the spheroids shrunk. Understanding how axonal spheroids grow—and how to restrict their growth—may help inform additional research about these structures and their role in Alzheimer’s disease.

A Potential New Treatment for Alzheimer’s and Other Diseases

Axonal spheroids are also significant to other neurodegenerative diseases, such as amyotrophic lateral sclerosis and Parkinson’s disease. The researchers hope this study will encourage more research about axonal spheroids, leading to new treatments for all of these diseases.

With this innovative Alzheimer’s treatment in focus, researchers plan to look at other signaling pathways that were identified in the study in hopes of understanding how to prevent axonal spheroid formation. This could potentially prevent Alzheimer’s disease and other neurodegenerative diseases.

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