Alzheimer's disease timeline shows neuronal changes start as a trickle, then become a torrent: Shots

Scientists have discovered that certain types of neurons are affected in the early stages of Alzheimer's disease.

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A study of cells taken from the brains of 84 cadavers suggests that there are two distinct stages of Alzheimer's disease, with one type of neuron being particularly vulnerable.

“There is an initial stage where the amount of pathology increases very slowly,” he says. ed line“Then you enter a more exponential phase where things suddenly get very, very bad,” said the senior researcher at Seattle's Allen Institute for Brain Science.

In this study, a small subset of neurons known as somatostatin inhibitory neurons When death begins in the early stages of Alzheimer's disease, Lane and a team of nearly 100 other scientists… report in a diary natural neuroscience.

“This was quite surprising,” Lane says, because these neurons have received relatively little attention from Alzheimer's disease researchers.

The findings suggest that treatments for Alzheimer's disease are most likely to help in the early stages of the disease, and that protecting vulnerable inhibitory neurons may be one strategy.

The results also show how scientists' understanding of Alzheimer's disease is changing with new tools and techniques that can reveal detailed information about millions of individual brain cells.

“They revealed what was going on that no one could have predicted just a few years ago,” he says. Dr. Richard HawesHe heads the National Institute on Aging, which has played a key role in funding research.

Track changes in brain cells

The study examined more than 3.4 million cells taken from the brains of people aged 65 and older who died. Some had healthy brains, while others were in various stages of Alzheimer's disease.

The research team focused on an area called the middle temporal gyrus, which is involved in language, memory, and vision.

By comparing cells taken at different stages of Alzheimer's disease, scientists were able to create a timeline of how the disease changes the brain.

“We measure every gene in each individual cell,” Liang says. “This allows us to not only identify those cells, but also look for changes in the cells that occur as a result of the disease.”

Some of the changes support previous research. For example, cells involved in immune function in the brain became more active.

Raine said artificial intelligence and new imaging and genetic techniques have enabled the team to look for other changes that were previously undetectable.

“We were looking for vulnerable cell populations, such as certain types of neurons that are particularly likely to be lost early in the disease,” Lane says.

The researchers had hoped to discover changes in excitatory neurons, which act like a car gas pedal by forming connections with distant areas of the brain and prompting other neurons to fire.

“But it turns out that the cells that were initially lost were actually part of the inhibitory neurons,” Liang says.

Inhibitory neurons act like the brakes on a car by forming connections with nearby excitatory neurons and controlling their activity.

A particular type of inhibitory neuron that appears to die early in Alzheimer's disease releases a chemical messenger called somatostatin, which is known to be reduced in Alzheimer's patients.

Somatostatin neurons help control the activity of brain networks involved in memory and thinking.

The loss of these cells can disrupt the delicate balance between inhibitory and excitatory neurons in the brain. Epilepsy and other brain diseases are thought to be the result of an imbalance.

“Perhaps the reason we lost these things was because [somatostatin] “Inhibitory neurons are overexcited, which may contribute to the disease,” Hodes says.

If so, Hodes says, treatment needs to start before too many inhibitory neurons are lost. And new research suggests it may be possible.

“The fact that there is a slow process early on gives us a great opportunity to intervene,” he says.