Researchers identify regions of genome involved in Alzheimer's

April 4 (UPI) -- An international team of researchers has identified 75 regions of the human genome associated with the development of Alzheimer's disease, including 42 never before linked with the common form of dementia, they said Monday.

After analyzing the genomes, or complete genetic data, for thousands of people, the researchers found 75 loci, or regions, of DNA involved in Alzheimer's, they reported in an article published Monday by the journal Nature Genetics.


Several of the identified regions of the genome are involved in the accumulation of amyloid-beta in the brain, which is known to cause Alzheimer's, according to the researchers.

In addition, they identified genes that affect production of a protein called tau that is found in brain cells. Changes in tau production also have been linked with Alzheimer's disease, the researchers said.

Based on their findings, the researchers have developed a genetic "risk score" for Alzheimer's, though it is still in the draft stage and is not yet ready for use in clinical practice, they said.


"Our knowledge of the genetics of AD common forms cannot allow it to be used as an individual diagnostic tool yet," study co-author Jean-Charles Lambert told UPI in an email.

"On the other hand, we show in our paper that this knowledge makes it possible in populations to define groups of individuals more or less at risk of developing the [disease]," said Lambert, research director at Inserm in Lille, France.

On Thursday, researchers working with the National Human Genome Research Institute announced that they had mapped a complete human genome for the first time.

This map could serve as a "reference," or guide, for researchers seeking to identify the genetic component of various diseases and traits, they said.

Amyloid-beta and tau have both been linked with Alzheimer's, the most common form of dementia in the United States, affecting some 6 million people, most of whom are age 65 years and older, according to the Alzheimer's Association.

However, it is not yet fully understood why some people have higher levels of amyloid-beta in their brains than others, placing them at higher risk for cognitive, or brain function, decline, Lambert said.

Most cases of Alzheimer's are thought to be caused by the interaction of different genetic and environmental factors, the latter of which include air pollution, research suggests.


In addition to identifying the genome regions behind amyloid-beta and tau development, Lambert and his colleagues also noted that many people with Alzheimer's also have modifications, or changes, in the genome that impact immune response, they said.

These changes affect the function of microglia, or the immune cells in the central nervous system that play a "trash collector" role by eliminating toxic substances, the researchers said.

The analysis also revealed that the tumor necrosis factor alpha-dependent signaling pathway, which plays a role in cell development, according to researchers.

The findings suggest that future clinical trials of therapies designed to treat Alzheimer's should focus on targeting amyloid-beta, microglial cells and the tumor necrosis factor alpha signaling pathway, they said.

They plan to validate the accuracy of their genetic risk score in future studies.

"This genetic knowledge will be the basis of personalized medicine" for Alzheimer's patients, Lambert said.

"This research is important today for the development of therapeutic approaches but in the not-so-distant future, for the clinical management of patients at the earliest stage," he said.

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