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Recently discovered Alzheimer's genes are a hope for future treatments



The study reveals that these genes, as well as others already identified, seem to work in tandem to control the bodily functions affecting the development of the disease.

"This is a powerful study and a step forward for our understanding of Alzheimer's disease," said neurologist Richard Isaacson, head of the prevention clinic for Alzheimer's. Alzheimer's disease in Weill Cornell Medicine.

"The discovery of these new genes allows clinicians to target them one day through therapeutic interventions," said Isaacson, who was not involved in the study. "It also gives us a better overview of the potential causes of Alzheimer's disease."

The results of the study will not change anyone's "daily life or medical practice," said Heather Snyder, senior director of medical and scientific operations at the Alzheimer's Association, who also was not involved in the new research.

"That said, they give us potentially useful information about bodily processes that can cause or interact with changes in Alzheimer's disease and other dementias," added Snyder.

Unprecedented numbers

Led by a team from the Hussman Institute for Human Genomics at the University of Miami, an international consortium of researchers analyzed data collected from four centers, two in the United States and two in the United States. in Europe, which make up the international project of genomic Alzheimer's.
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The study, published Thursday in the journal Nature Genetics, was the second genome-wide association study conducted by the group on individuals with known Alzheimer's disease compared to a control group. The first study, published in 2013, looked at nearly 75,000 people and identified 11 "loci" or gene locations, the existence of which was previously unknown to the development of Alzheimer's disease.

By increasing the number to 94,000, the new study adds 30% more data to the analysis, allowing researchers to check 20 previously found genes and add four more.

The way the new genes – IQCK, ACE, ADAMTS1 and WWOX – and a previously discovered gene called ADAM10 affect the development of Alzheimer's disease is being studied. But once their specific functions are understood and reviewed, the researchers say that they will be able to start developing potential drug targets.

"Alzheimer's disease is a complex disease, it's not like Huntington's disease or Parkinson's, where a gene is impaired and you contract the disease," said Dr. Margaret Pericak-Vance, Principal author, director of the Hussman Institute.

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"With Alzheimer's, there are several genes that work together," said Pericak-Vances. "We were trying to discover the very rare genetic variants that could contribute to Alzheimer's disease, and we could not do it before." We just had not the size of the sample to do it ".

The study validated the previously discovered role of immune system and amaloid genes in the development of Alzheimer's disease, said Rudy Tanzi, professor of neurology at Harvard, director of the Alzheimer's Genome project and member of the international consortium.

"We had seen the amaloid at first, but that was not checked in a [genome-wide association study], "Tanzi said. So, I think that one exciting thing is that it brings us back to the amyloid as a major player.

"I should also say that we also find that innate immunity is innate immunity, in addition to amyloid," said Tanzi. "In this study, we are seeing even more innate immune genes affecting susceptibility to neuroinflammation."

Sensitivity to neuroinflammation is essential, says Tanzi, "because by late afternoon, plaques and tangles can clear the way, but it's neuroinflammation that kills enough neurons to cause dementia."

Now, having more than a dozen gene targets on the links between immunity and Alzheimer's disease should, according to Mr. Tanzi, "truly facilitate the discovery of newborns." 39, a new drug ".

Precision medicine

The increase in the size of the sample allowed researchers to discover "gene nuclei" that could affect the development of Alzheimer's disease. "And some of these genes could have more of a function," said lead author Brian Kunkle, an associate scientist at the Hussman Institute.

"They can increase risk through different routes of disease transmission," said Kunkle. "The risk prediction and treatment of each individual will depend on the type of change that a person has in each of these 25 genes or other biomarkers."

Isaacson said the work in progress could lead to "precision medicine at its best".

"A person can take many different paths to get to Alzheimer's disease," said Isaacson. "If we can determine a person's path by identifying certain genes, we can target specific interventions that may work preferentially for that particular person."

Kunkle is cautiously optimistic about when this could happen.

"It's hard to say if it will help a person with Alzheimer's now," he said. "Hopefully, treatments will be developed for family members who may have these genes that endanger them."


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