close up of gloved scientist's hands holding a screen displaying DNA patternsShare on Pinterest
New research pinpoints 75 genes associated with Alzheimer’s risk. PER Images/Getty Images
  • An international team of researchers has identified 75 genes linked to an increased risk of Alzheimer’s disease, including 42 genes previously not associated with the disease.
  • They also discovered a connection between the protein Tumour Necrosis Factor alpha (TNF-alpha) and Alzheimer’s disease.
  • Researchers believe their findings may help illuminate potential therapeutic pathways.

Although Alzheimer’s disease does not always have a clear genetic cause, genes are considered a risk factor for the disease. And past research has identified certain genes associated with Alzheimer’s.

Now, an international team of researchers from eight partner countries has found a total of 75 genes linked to an increased risk of developing Alzheimer’s. Of those genes, 42 are new genes that had not previously been associated with the disease.

The results from this study appear in the journal Nature Genetics.

For this study, researchers compared the genes of more than 111,000 people with Alzheimer’s disease to those of more than 677,000 people without the condition.

Medical News Today had the chance to speak with Dr. Jean-Charles Lambert, research director of INSERM, the French National Institute of Health and Medical Research in Paris, and co-lead author of this study. He said this research was an opportunity to understand why some people develop a disease like Alzheimer’s disease.

The study looked for differences in genes between people with Alzheimer’s disease and those without the condition, in what is known as a genome-wide association study.

In the study, Dr. Lambert explained, “we rely on strong indices [that show] that the genetic component of Alzheimer’s disease is particularly high and that support the existence of numerous genetic susceptibility factors.”

“This implies that these genetic factors participate in the deleterious mechanisms that develop over the years preceding the clinical expression of the pathology. Genetic research is first and foremost basic research to understand in the most intimate way possible what goes wrong in our brains as we age [that] can lead to Alzheimer’s.”

During their research, the team also discovered a connection between the TNF-alpha protein and Alzheimer’s disease. TNF-alpha is a small protein called a cytokine that works with the body’s immune system and helps protect the body by triggering inflammation.

Researchers found multiple genes associated with Alzheimer’s disease involved in a blockage of TNF-alpha signaling.

“The TNF pathway is undoubtedly a pathway that will be studied as a therapeutic approach of interest for Alzheimer’s disease,” Dr. Lambert said when asked how TNF-alpha protein may play a role in future therapy development for Alzheimer’s.

“I have no doubt that many researchers and pharmaceutical companies will look into this possibility, especially since there are already treatments targeting this pathway in other diseases.”

Dr. Heather Snyder, Alzheimer’s Association vice president of medical and scientific relations, who was not involved in the study, also spoke to MNT. She said previous research has shown TNF-a, or TNF-alpha, signaling plays a very well-known role in inflammation, and may also have many other roles in the brain.

“More research will need to be conducted to understand the complicated role that TNF-a signaling may play in Alzheimer’s, though there are already some clinical trials that are addressing this question,” she continued. “In 2018, the Alzheimer’s Association, through its Part the Cloud global research program, funded an early-stage clinical trial of a promising TNF-targeting drug for the treatment of Alzheimer’s.”

Additionally, the team also uncovered evidence suggesting a connection between dysfunctioning microglia and Alzheimer’s. Microglia are brain cells that help defend the central nervous system against bacteria and viruses and regulate the removal of waste cells and other matter from the brain.

For the next steps in this research, Dr. Lambert explained that the genetic component of Alzheimer’s disease is not yet fully characterized and they are therefore working to better define it. “The aim is to increase the number of cases studied, but also to extend these analyses to other multi-ancestry populations that are still little studied at present,” he added.

He also believes that these findings help further illuminate pathways that clinicians can take toward the development of therapeutics for helping to delay and/or prevent Alzheimer’s.

“We now know that there is not just one pathway — a pathophysiological process — to arrive at the development of the disease,” Dr. Lambert explained.

“We will likely need polytherapies [i.e. combined therapy] depending on the pathways each patient takes to eventually develop the disease. These polytherapies will therefore probably have to be adapted to each of them and likely to their genetic background. This will open up the field of personalized medicine in [Alzheimer’s disease], but we’re not there yet.”

“In the short term, our data tell us that the pathophysiological pathways for which we are already developing therapeutic approaches are good targets — which is reassuring — and that there are new pathways to explore, [which] were not known until our study,” he added.

Dr. Snyder agreed, stating that this study combined multiple research groups together in a way that helps clinicians do more, [work] faster, and significantly expand their knowledge of potential genes of interest.

“This study gives us hints of where to look at the biology of neurodegeneration — such as the immune system and the cell transport system,” she added. “A better understanding of these genes and the biologies they’re associated with will help inform precision medicine approaches in the future for those with genetic markers for Alzheimer’s.”

“While exciting, this work is still early and many of the new genetic targets identified need to be validated in a group that is more ancestrally diverse.”

– Dr. Snyder