The study reveals that Alzheimer’s disease damages the brain in two distinct phases

An analysis of the genetic activity of brain cells in individuals who have died with Alzheimer’s disease has revealed that the disease progresses in two stages; a slow increase in inflammation, followed by more rapid degeneration.

Importantly, the first of these phases is limited in scope and occurs before symptoms such as memory loss appear, indicating that opportunities for diagnosis and treatment could occur at an earlier stage than at present .

The second stage results in a more pronounced level of destruction, with the noticeable build-up of plaques and protein tangles coinciding with severe neuronal damage resulting in a loss of cognitive function.

The researchers, led by teams from the University of Washington and the Allen Institute for Brain Science, profiled the genetic activity of individual cells in an area of ​​the brain known as the middle temporal gyrus, where key functions are located of memory, language and vision. handled

“This approach provides a comprehensive understanding of the specific and highly granular cell types affected throughout the course of the disease, where the affected cells are located in the tissue microarchitecture, and when they are affected as the disease progresses,” write the researchers in their published article.

The team analyzed the brains of 84 people who had died of Alzheimer’s and had an average age of 88. These readings and measurements were then compared to brains from non-Alzheimer’s donors to identify critical differences.

In addition to the findings of different pathological phases, the researchers discovered specific damage to the cognitively crucial inhibitory neuron in the first phase. This may be how problems in neural circuits are initially triggered, the team suggests.

In the past, excitatory neurons, those that activate other neurons, have been linked to Alzheimer’s disease. Inhibitory neurons are those that turn off or calm down neurons, so the Alzheimer’s connection here is new and interesting.

The findings provide important contributions to a comprehensive, publicly available map of Alzheimer’s damage to the brain known as the Seattle Alzheimer’s Disease Brain Cell Atlas (SEA-AD). The hope is that if we follow this path of neuron destruction more closely, we can better understand how Alzheimer’s is taking hold: what stops it and what allows it to happen.

As our scientific technology becomes more advanced and more capable, we’re learning more about the complexities of Alzheimer’s, whether it’s triggers elsewhere in the body, links to other diseases, or a previously undiscovered hidden early stage. .

“The results fundamentally alter scientists’ understanding of how Alzheimer’s damages the brain and will guide the development of new treatments for this devastating disorder,” said Richard Hodes, director of the NIH’s National Institute on Aging, who did not participate directly in the study.

The research was published in Neuroscience of nature.

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