Alzheimer’s: why memory neurons are most vulnerable to the disease

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American researchers have developed microdissection technology for neurons to understand why those responsible for memory and memory are most vulnerable to Alzheimer’s disease. This discovery could lead to new therapeutic treatments.

Affecting almost 5 million people in the United States, Alzheimer’s disease is the most common form of age-related dementia. Still incurable at present, this neurodegenerative disease slowly, gradually, and irreversibly causes dysfunction and then the death of nerve cells in the brain.

Two phenomena are involved. First, the formation of amyloid plaques in the brain. Responsible for impairing the mental functions of patients, they accumulate abnormally in the neurons, causing progressive and irreparable damage to the brain. Then follow neurofibrillary tangles which obstruct the interior of neurons, those of the entorhinal cortex, responsible for the formation of memories and memory.

Genetic abnormalities

Until now, researchers have not known why memory neurons are particularly vulnerable to neurofibrillary tangles. “We have accumulated a huge knowledge of the mechanisms that produce amyloid plaques,” explains Jean-Pierre Roussarie, senior research associate in Paul Greengard’s molecular and cellular neuroscience laboratory. But what happens downstream of amyloid buildup, and how these plaques trigger neurofibrillary tangles in vulnerable neurons, has remained an enigma.”

A team from Rockefeller University in New York (United States) explains that they may have found the answer. They have developed a technology called BacTRAP that can catalog proteins in specific populations of neurons in mice. This is a microdissection of neurons that has allowed researchers to isolate vulnerable neurons and analyze how they genetically differ from more resistant brain cells. A team from Princeton University, led by Olga Troyanskaya, then designed computer algorithms to help the team focus only on the genetic abnormalities that may be most relevant to neurodegeneration.

“The goal was to form an overview, rather than a list of genes,” said Marc Flajolet, co-author of the study. It is only through these sophisticated data analysis frameworks that we can get to the bottom of something as complicated as the neurodegenerative cascade of Alzheimer’s disease.”

Hope for new treatments

The results thus highlighted a series of genes probably involved in the fact that the neurons of the entorhinal cortex are easy targets for degeneration. One of them, produced by the protein PTBP1, also plays a major role in the early stages of Alzheimer’s disease. “Once we have found what makes neurons more vulnerable, it could lead to multiple avenues to reduce their vulnerability,” says Professor Roussarie.

According to the latter, this discovery could lead to the development of new prevention and treatment strategies specifically targeting neurofibrillary tangles. “The diversity of neurons was simply not considered before. Many people are studying neurofibrillary tangles, but it is only now that we are starting to tackle them through the prism of the vulnerability of neurons”, concludes Jean-Pierre Roussarie.