Dozens of genetic risk factors that Alzheimer’s identified by scientists

Dozens of genes that increase the risk of Alzheimer’s disease have been identified. Many fuel rogue brain proteins known as amyloid beta and tau, hallmark signs of the disease, say scientists. They collect in clumps and tangles respectively, destroying neurons. The breakthrough offers hope of new treatments for the memory-robbing disease.

Researchers at The Pasteur Institute of Lille in France say their findings mean people could be screened for Alzheimer’s disease in middle age and given cutting edge gene therapy. DNA mapping linked 75 regions, or “loci,” of the genome to the illness, 42 of which have never previously been implicated.

The findings are based on almost 800,000 people across Europe.

“Following this major discovery, we characterized these in order to give them meaning in relation to our clinical and biological knowledge, and thereby gain a better understanding of the cellular mechanisms and pathological processes at play,” says study coordinator Jean-Charles Lambert, in a statement.

Alzheimer’s is believed to be triggered by a combination of environmental factors, such as lifestyles. Gene mutations predispose certain individuals. Dementia cases worldwide are expected to triple in the next three decades to more than 150 million. Current medications only target the symptoms – not the cause.

The study included 111,326 people who had either been diagnosed themselves or had close relatives who had. They were compared with 677,663 healthy controls.

“A recent study estimated fewer than 100 causal common variants may explain the entire Alzheimer’s risk. If that estimate is correct, then our study might have already characterized a large proportion of this genetic component,” says Lambert.

Accumulation of amyloid-beta and tau is a common feature in brain tissue from people who have died with Alzheimer’s disease. The study confirms some of the genes are involved in production of the proteins. Others block immune cells called microglia. They lie in the central nervous system and help clear the build-up of these toxic substances.

Finally, it shows for the first time a harmful body chemical called TNF-alpha (tumor necrosis factor-alpha) may be to blame for the advance of Alzheimer’s. The international team called for clinical trials of drugs targeting the amyloid pre-cursor protein and TNF-alpha.

They also advised continuation of microglial cell research initiated a few years ago – and the targeting of the TNF-alpha signaling pathway.

A genetic risk score based on the findings has been developed which can predict Alzheimer’s disease within three years of clinical manifestation of cognitive impairment.

“While this tool is not at all intended for use in clinical practice at present, it could be very useful when setting up therapeutic trials in order to categorize participants according to their risk and improve the evaluation of the medications being tested,” says Lambert.

The researchers now plan to validate and expand the results in an even broader group. They are developing numerous cellular and molecular biology approaches to determine their roles in Alzheimer’s disease.

Gene editing replaces a target area of DNA. It has been described as a “cut and paste” tool, removing mutations that arise when genes fuse to make an unhealthy hybrid.

The study is published in Nature Genetics.

Report by Mark Waghorn, South West News Service

The contents of this website do not constitute advice and are provided for informational purposes only. See our full disclaimer

About the Author

Steve Fink

Steve Fink is the Editor-in-Chief of BrainTomorrow.com, GutNews.com and StudyFinds.com. He is formerly the Vice President of News Engagement for CBS Television Stations’ websites, and spent 20 years with CBS.

Leave a Reply

Your email address will not be published.