Brain cells most vulnerable to Alzheimer’s disease first identified by scientists

Scientists have identified brain cells that are most vulnerable to Alzheimer’s disease for the first time in what is called the “holy grail” of dementia studies.

Brain cells are located in a region known as the entorhinal cortex, which controls memory, navigation and perception of time and are the first to be killed by the disease.

The researchers hope the findings could be used to develop a new and more development-oriented approach to developing therapies to slow or prevent the spread of Alzheimer’s disease.

Brain cells are particularly prone to toxic agglomerations or “tangles” of a protein called tau that destroys them from within.

The lead co-author, Professor Martin Kampmann, of the Institute for Neurodegenerative Diseases, said targeting them could stop the disease.

Brain tissue analysis found that the specific group of cells disappears very early – followed by a similar subset in the upper frontal gyrus.

This is an area of ​​gray matter responsible for higher cognitive functions, such as thinking, problem solving, planning and working memory – used in performing tasks.

The findings published in Nature Neuroscience are a “holy grail” of dementia research.

Prof. Kampmann explained: “We know which neurons die first in other neurodegenerative diseases, such as Parkinson’s disease and motor neuron disease – but not Alzheimer’s.

“If we understood why these neurons are so vulnerable, maybe we could identify interventions that could make them and the brain as a whole more resistant to disease.”

Alzheimer’s is caused by tau and amyloid – another dishonest protein that builds up in plaques or groups outside brain cells.

Yours was described as the “bullet”. The team at the University of California, San Francisco says some brain cells give way years before symptoms appear – opening a “window of opportunity.”

Lead co-author Prof. Lea Grinberg said: “The belief in the field was once these garbage proteins are there, it’s always a ‘finished game’ for the cell.

“But our lab found that was not the case.

“Some cells end up with a high level of tangles in your disease until the disease progresses, but for some reason they do not die.

“It has become a pressing question for us to understand the specific factors that make some cells selectively vulnerable to Alzheimer’s disease, while other cells seem able to withstand it for years, if not decades.”

The researchers studied the tissues in two brain banks of dozens of people who died at various stages of Alzheimer’s disease in the United States and Brazil.

A technique called single-nucleus RNA sequencing then allowed the grouping of neurons based on patterns of gene activity.

In both the entorhinal cortex and the superior frontal gyrus, these vulnerable cells were distinguished by their expression of a protein called RORB.

Under a microscope, they confirmed that these neurons actually die at the beginning of the disease. Also, accumulate your messes earlier than neighbors without RORB.

Co-first author Kun Leng, a doctoral student in Prof. Kampmann’s laboratory, said: “These findings support the view that your accumulation is a critical factor in neurodegeneration.

But we also know from other data from the Grinberg laboratory that not every cell that accumulates these aggregates is equally susceptible.

He intends to continue to analyze the factors underlying the selective vulnerability of RORB neurons using the genetic editing technology that Kampmann Laboratory has developed.

It is unclear whether RORB itself causes selective cell vulnerability. But protein provides a valuable new molecular “handle.”

This will help you understand what makes these cells susceptible to Alzheimer’s – and how they could be reversed.

Co-lead author Kun Leng of the University of California, San Francisco said: “Our discovery of a molecular identifier for these selectively vulnerable cells gives us the opportunity to study in detail exactly why it yields to your pathology – and what could do to make them more resilient.

This would be a completely new and much better approach to developing therapies to slow or prevent the spread of Alzheimer’s disease.