Scientists have discovered the true cause of Alzheimer’s disease

The formation of amyloid plaques in the brain is a hallmark of Alzheimer’s disease. (CREDIT: Creative Commons)

The formation of amyloid plaques in the brain is a hallmark of Alzheimer’s disease. But drugs designed to reduce the buildup of these plaques have so far produced mixed results at best in clinical trials.

However, researchers at Yale University have found that swelling caused by a by-product of these plaques may be the true cause of the debilitating symptoms of the disease, they report Nov. 30 in the journal Nature. And they identified a biomarker that could help doctors better diagnose Alzheimer’s and provide a target for future treatments.

According to their findings, each plaque formation can cause an accumulation of spheroidal swellings along hundreds of axons — thin cellular wires that connect brain neurons — next to deposits of amyloid plaques.

The researchers found that the tumor is caused by the gradual accumulation within cells of organelles known as lysosomes, which are known to digest cellular waste. The researchers say that as tumors get bigger, they can blunt the transmission of normal electrical signals from one area of ​​the brain to another.

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The researchers say that this accumulation of lysosomes causes swelling along the axons, which in turn causes the devastating effects of dementia.

“We have identified a potential signature of Alzheimer’s disease that has functional implications for brain circuitry, with each spheroid having the potential to disrupt the activity of hundreds of neural axons and thousands of interconnected neurons,” said Dr. Jaime Grutzendler, 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.

In addition, the researchers found that a protein in lysosomes called PLD3 causes these organelles to grow and stick together along axons, eventually causing the axons to swell and disrupt electrical conduction.

When they used gene therapy to remove PLD3 from neurons in mice with an Alzheimer’s disease-like condition, they found that it resulted in a dramatic reduction in axonal swelling. This, in turn, normalized the electrical conduction of the axons and improved the function of neurons in the areas of the brain connected by these axons.

The researchers say PLD3 could be used as a marker to diagnose Alzheimer’s disease risk and become a target for future treatments.

Swelling of the surrounding amyloid plaques (light blue) in patients with Alzheimer’s disease may be the cause of dementia symptoms. (TEACHER: Yale University)

“It may be possible to eliminate this disruption of electrical signals in axons by targeting PLD3 or other molecules that regulate lysosomes, regardless of the presence of plaques,” Grutzendler said.

Who has Alzheimer’s disease?

• In 2020, 5.8 million Americans were living with Alzheimer’s disease.

• Young people can develop Alzheimer’s disease, but it is less common.

• The number of people living with the disease doubles every 5 years after they reach the age of 65.

• By 2060, this number is predicted to nearly triple to 14 million people.

• Symptoms of the disease may first appear after age 60, and the risk increases with age.

What is known about Alzheimer’s disease?

Scientists don’t yet fully understand what causes Alzheimer’s disease. There is probably not one cause, but several factors that can affect each person differently.

• Age is the best known risk factor for developing Alzheimer’s disease.

• Family history – Researchers believe that genetics may play a role in the development of Alzheimer’s disease. However, genes are not equal to fate. A healthy lifestyle can help reduce the risk of developing Alzheimer’s disease. Two large, long-term studies show that adequate physical activity, a nutritious diet, limiting alcohol intake, and not smoking can help people.

• Changes in the brain can begin years before the onset of the first symptoms.

• Researchers are studying whether education, diet and environment play a role in the development of Alzheimer’s disease.

• There is growing scientific evidence that a healthy lifestyle, which has been shown to prevent cancer, diabetes, and heart disease, can also reduce the risk of subjective cognitive decline.

What is the burden of Alzheimer’s disease in the United States?

• Alzheimer’s disease is one of the top ten causes of death in the US.

• 6th leading cause of death among adults in the US.

• Fifth leading cause of death among adults aged 65 and over.

• In 2020, approximately 5.8 million Americans aged 65 and over had Alzheimer’s disease. By 2060, this number is predicted to nearly triple to 14 million people.

In 2010, spending on Alzheimer’s disease was predicted to fall from $159 billion to $215 billion. By 2040, these costs are projected to rise from $379 billion to more than $500 billion a year.

Alzheimer’s death rates are on the rise, in contrast to cardiovascular disease and cancer deaths, which are declining.

It has been shown that dementia, including Alzheimer’s disease, is underreported on death certificates and therefore the proportion of older people dying from Alzheimer’s disease may be significantly higher.

For more science news, visit our New Discoveries section at The bright side of the news.

Note: Materials provided above by Yale University. Content can be edited for style and length.

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