Alzheimer's: Brain cells can modify their DNA and promote the arrival of the disease

Brain cells can modify their DNA, unlike most cells in our body, thus promoting the onset of Alzheimer's. This discovery could allow a potential short-term treatment against this disease.

US scientists at the Sanford Burnham Prebys Medical Discovery Institute (SBP) have identified a recombination of genes in neurons, called somatic recombination, producing thousands of new gene variants in the brain of a patient with Alzheimer's disease. This study was published in the journal Nature.

"A historical study"

"This is potentially one of the greatest discoveries in the field of molecular biology for years," said Geoffrey Faulkner, a molecular biologist at the University of Queensland in Brisbane, Australia, who did not participate in the event. research. "This is a historical study," confirms clinical neurologist Christos Proukakis from University College London.

To find definitive evidence for somatic recombination in the brain, the researchers analyzed neurons from the brains of six healthy elderly people and seven patients with the most common non-inherited form of Alzheimer's disease.

They then tested whether the cells harbor different versions of the amyloid precursor protein (APP) gene, the source of the plaques in the brains of people with Alzheimer's disease. "We used new approaches to study the APP gene that gives rise to amyloid plaques, a pathological feature of the disease," said Jerold Chun, lead author of the article. "Gene recombination has been discovered both as a normal process for the brain and a process that goes wrong in Alzheimer's disease."

Potentially revolutionary results

The researchers found that the neurons of Alzheimer's patients contained about six times more varieties of the APP gene than the cells of healthy people. They identified 11 mutations that occur in the rare hereditary forms of the disease. "Rather than having a consistent pattern that stays with us throughout life, neurons have the ability to change that," says the US researcher.

"These findings could fundamentally alter our understanding of the brain and Alzheimer's disease," said Jerold Chun. "If we imagine DNA as a language that every cell uses to communicate, we find that in neurons, a single word can produce several thousand new, previously unknown words, much like an embedded secret code. to our normal code.The secret code is used in healthy brains but seems to be disrupted in the brains of those with Alzheimer's disease. "

Potential short-term treatment of Alzheimer's

Scientists have discovered that the process of gene recombination requires an enzyme called reverse transcriptase. This is the same type of enzyme that HIV uses to infect cells. Although there is no medical evidence that HIV causes Alzheimer's disease, existing antiretroviral antiretroviral therapy may also help stop the recombination process and be explored as a new Alzheimer's treatment. Scientists have noted the relative absence of this disease in elderly HIV patients on antiretroviral therapy, which supports this approach.

"Our results provide a scientific rationale for immediate clinical evaluation of antiretroviral therapy for HIV in people with Alzheimer's disease," confirmed Jerold Chun. "Such studies could also be useful for high-risk populations, such as people with rare genetic forms of Alzheimer's disease."