Alzheimer’s disease may cause brain damage in two stages, a new study says. The study was supported by the National Institutes of Health (NIH) uses sophisticated brain mapping methods and is published in Nature Neuroscience. The researchers say they have uncovered this new perspective, saying the early stage occurs slowly and quietly, before people suffer from memory problems, and affects only a few vulnerable cell types.

However, in contrast, the second and late stage produces more extensive damage and correlates with the onset of symptoms and the rapid accumulation of plaques, tangles, and other symptoms of Alzheimer’s.

Richard J., MD, director of the NIH National Institute on Aging. “One of the challenges in diagnosing and treating Alzheimer’s is that much of the damage to the brain occurs before symptoms appear,” Hodes said. The ability to detect these early changes means that, for the first time, we can see what is happening in a person’s brain during the early period of the disease.

“The results fundamentally change scientists’ understanding of how Alzheimer’s damages the brain and will guide the development of new treatments for this devastating disorder.”

For the study, researchers analyzed the brains of 84 people and the results suggest that damage to a type of cell called an inhibitory neuron during the early stages may lead to neural circuit problems that lead to the disease. Are. In addition, the study confirmed previous findings about how Alzheimer’s damages the brain and identified several new changes that occur during the course of the disease.

Scientists used advanced genetic analysis tools to specifically study cells of the middle temporal gyrus, a part of the brain that controls language, memory and vision.

The gyrus has been shown to be sensitive to many of the changes traditionally observed during Alzheimer’s. It’s also the only part of the brain that researchers have completely mapped for control donors. By comparing donor data to people with Alzheimer’s and controls, scientists created a genetic and cellular timeline of what happens throughout the course of the disease.

Traditionally, studies have shown that the damage caused by Alzheimer’s occurs in several stages, including increased levels of cell death, inflammation, and the accumulation of proteins in the form of plaques and tangles.

In contrast, this study shows that the disease changes the brain in two “eras” or stages, with many of the traditionally studied changes occurring more rapidly during the second stage. This coincides with the appearance of memory problems and other symptoms.

The results also show that early changes occur slowly and “quietly” in the first phase, before any symptoms appear. These changes include slowed accumulation of plaque, activation of the brain’s immune system, damage to the cellular insulation that helps send signals to neurons, and the death of cells called somatostatin (SST) inhibitory neurons.

The final discovery was surprising to the researchers. Traditionally, scientists have thought that Alzheimer’s primarily results from damage to excitatory neurons, which send active nerve signals to other cells. Inhibitory neurons send calming signals to other cells. The paper’s authors speculated about how the loss of SST inhibitory neurons might trigger changes in the brain’s neural circuitry that lead to the disease.

More recently, a separate NIH-funded brain mapping study by MIT researchers found that a gene called REELIN may be linked to the vulnerability of certain neurons to Alzheimer’s. It also revealed that star-shaped brain cells, called astrocytes, may provide resilience or resistance to damage caused by disease.

Researchers analyzed the brains that are part of Seattle alzheimer’s disease The Brain Cell Atlas (link is external) (SEA-AD), which is designed to create a highly detailed map of the brain damage that occurs during the disease. The project is led by Mariano I. Gabito, Ph.D., and Kyle J. Allen from the Allen Institute, Seattle. Travaglini, Ph.D. was did. Scientists used tools developed as part of NIH’s Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative – Cell Census Network (BICCN) to study more than 3.4 million brain cells from donors who died at various stages of Alzheimer’s disease. Used. Tissue samples were obtained from the Adult Changes in Thought (link is external) study and the Alzheimer’s Disease Research Center at the University of Washington.

“This research demonstrates that powerful new technologies provided by NIH’s Brain Initiative are changing the way we understand diseases like Alzheimer’s,” said John Nagai, PhD, director of The Brain Initiative. With these tools, scientists were able to detect the earliest cellular changes that occur in the brain to build a more complete picture of what happens throughout the course of the disease.

“The new knowledge provided by this study may help scientists and drug developers around the world develop targeted diagnostics and treatments for specific stages of Alzheimer’s and other dementias.”

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