Yale Researchers May Have Found the True Cause of Alzheimer’s Disease

Yale Researchers announced at the very end of November 2022 that they may have finally identified the true cause of Alzheimer’s disease. Alzheimer’s is the most common type of dementia afflicting people in the United States today. Before this research study, it was known that plaque accumulations in the brain are associated with Alzheimer’s disease. Yale researchers have concluded through their study that it is not so much the buildup of plaque but the fact that axons in the brain swell, preventing the transmission of signals from one part of the brain to another.

The technical summary of the researcher’s study is as follows:

The formation of plaques can cause the accumulation of spheroid-shaped swellings along axons near the amyloid plaque deposits. The swellings are caused by lysosomes, which digest cellular waste. As the swelling enlarges, it can block the transmission of signals from one area of the brain to another.

What Are Axons?

If you are like many seniors, caregivers for seniors, and others, you likely have not heard of axons in the brain. Therefore, before we dive further into the results of this significant research study, we provide an overview of axons in the human brain.

Axons are the long, thin projections of cells that transmit electrical signals from one part of the brain to another. Axons carry nerve impulses – in other words, messages – from one neuron or nerve cell to another. Axons form what is known as a neural network and are essential for coordinating the activities of the brain and body.

Axons serve as a conduit between neurons, allowing a signal to pass from one neuron to another for neurons to communicate. For example, axons can connect neurons within the same brain region, but they can also connect neurons located in different regions or even different parts of the body. The cell bodies receive information from sensory organs or other neurons, while the axons transmit this information to other cells, where it is then processed.

At their most basic level, axons act like electrical wires; they conduct an electrical current through specialized proteins, known as ion channels, which allow positively charged ions to enter the cell and cause depolarization. This depolarization causes an action potential, basically, an electrochemical rush that propagates along the length of the axon until it arrives at its target destination, where it triggers a response. Coordinated muscle movement is an example of such a response.

The structure and composition of axons vary depending on their function; some are short and stubby, while others may be several feet long. Some axons can stretch up to several yards in length. The thickness of an axon can range anywhere from 0.1 micrometers to over 50 micrometers thick, allowing them various capabilities, such as supporting very fast transmission speeds or increasing strength and durability when needed by enlarging their size.

In addition, many research studies have revealed various layers within every axon called myelin sheaths. These help increase conduction speed by insulating and protecting them against external disturbances, like temperature changes or mechanical vibrations. Furthermore, these myelin sheaths can increase exponentially over time, leading to faster conduction rates if needed for certain processes by forming more layers around them.

All in all, axons are arguably one of the most important components found within our brains. Without them, communication would not be possible between different regions or parts of our bodies, leaving us unable to regulate any movement or thought process.

Formation of Plaques in the Brain in Advance of Alzheimer’s Disease

The formation of amyloid plaques in the brain is considered to be a hallmark of Alzheimer’s disease. Medications have been designed to attempt to address these buildups in the brain. However, these medications have so far yielded mixed results in clinical trials.

As noted at the start of this article, Yale researchers have found that swelling caused by a byproduct of these plaques may be the true cause of the debilitating symptoms of Alzheimer’s disease. The Yale researchers reported their findings in the journal Nature. As a result of their study, researchers have identified a biomarker that may help physicians better diagnose Alzheimer’s. In addition, this biomarker may also provide a target for future therapies.

According to their findings, each formation of plaque can cause an accumulation of what they describe as spheroid-shaped swellings along hundreds of axons. These swellings occur near amyloid plaque deposits.

The swellings are caused by the gradual accumulation of what is known scientifically as organelles within cells. These species are called lysosomes. Lysosomes are known to digest cellular waste, researchers found. As the swellings enlarge, they can blunt the transmission of normal electrical signals from one brain region to another.

Researchers explained that the pileup of lysosomes causes swelling along axons. In turn, this swelling triggers the devasting effects of dementia, specifically Alzheimer’s.

“We have identified a potential signature of Alzheimer’s which has functional repercussions on the brain circuitry, with each spheroid having the potential to disrupt activity in hundreds of neuronal axons and thousands of interconnected neurons,” explained Dr. Jaime Grutzendler, Dr. Harry M. Zimmerman, Dr. Nicholas, and Viola Spinelli Professor of Neurology and Neuroscience at the Yale School of Medicine. He is the senior author of the study.

The researchers also discovered that a protein in lysosomes, known as PLD3, caused these “organelles” to grow and clump together along axons. This ultimately leads to the swelling of axons and the breakdown of electrical conduction between different parts of a person’s brain.

Researchers indicate that PLD3 may be used as a marker in diagnosing the risk of Alzheimer’s disease and provide a target for future therapies. “It may be possible to eliminate this breakdown of the electrical signals in axons by targeting PLD3 or other molecules that regulate lysosomes, independent of the presence of plaques,” Grutzendler explained.

In conclusion, while the results of this research certainly are positive, there remains no known cure for Alzheimer’s disease. With that said, dementia-related research studies have announced promising results in the past year, which suggest that a cure may be in the offing in the not-too-distant future.