42 New Genes Have Been Linked to an Increased Risk of Alzheimer's Disease, According to 'Landmark' Study

In the largest Alzheimer's study to date, researchers find new genes and pathways involved in development of the disease.

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The number of genes involved in Alzheimer's is more than double what scientists previously estimated, according to the findings of the largest genetic study of the disease to date.

Researchers have discovered 42 new genes associated with the development of Alzheimer's, according to study published in the journal Nature Genetics. The findings of the landmark study, which involved research centers in eight partner countries, including the United Kingdom, the United States, Australia, and countries across Europe, suggest a future where doctors may be able to more accurately predict whether individual patients are genetically predisposed for Alzheimer's disease.

"This study more than doubles the number of identified genes influencing risk for the more common form of Alzheimer's disease. It provides exciting new targets for therapeutic intervention and advances our ability to develop algorithms to predict who will develop Alzheimer's in later life," Rebecca Sims, MD, a senior research fellow at Cardiff University and UK Dementia Research Institute co-investigator, as well as co-leader of the study, said in a statement issued by researchers.

Here's a closer look at the significance of the study and its findings.

Study Scope and Findings

The most common form of dementia, Alzheimer's, affects about 5.8 million Americans, and the number of cases is expected to nearly triple by 2050.

The sweeping new study sought to identify the genetic risk factors involved in Alzheimer's disease. To do that, researchers studied the genomes of 111,326 people diagnosed with Alzheimer's and compared their findings to 677,663 people without Alzheimer's to identify differences in genetic makeup. This type of study is known as a genome wide association study (GWAS), and the sheer number of study subjects involved made this research effort the largest GWAS to date. The last GWAS effort involved about 22,000 people with Alzheimer's.

"We mainly increased the number of samples because it directly correlated to the number of cases we can analyze," Jean-Charles Lambert, PhD, interim research director and neuroscientist at the Université de Lille and lead author of the study, told Health.

The study found 75 gene variations related to Alzheimer's. Of those 75, there were 33 already known from previous genetic studies and 42 newly found to be associated with the development of Alzheimer's.

This discovery of the additional genes connected to Alzheimer's development is meaningful because, while lifestyle factors influence development of the disease, between 60% and 80% of Alzheimer's risk is based on our genetics, according to the statement issued by the research team.

Based on the study results, researchers devised a genetic risk score that can be used to "determine how likely patients with cognitive impairment will, within three years of first showing symptoms, go on to develop Alzheimer's disease." The risk score, however, is not meant to be used in clinical practice by physicians just yet. For the moment, researchers hope the score can be used to help improve the evaluation of new drugs in clinical trials. And then further down the road, scientists hope the findings of the study will help identify people in the population who may be at greatest risk of developing Alzheimer's before the disease sets in.

The new study also showed for the first time that "a specific biological signaling pathway involving TNF-alpha, a protein with an important role in inflammation and the immune system, is implicated in Alzheimer's," according to the researchers' statement. "Additionally, there is more evidence that the dysfunction of microglia, immune cells in the brain that are responsible for eliminating toxic substances, contribute to disease pathology."

This finding is also important in the effort to understand Alzheimer's and its progression.

"Components of our immune system have a big role to play in the development of the disease. For example, immune cells in the brain known as microglia are responsible for clearing out damaged tissue, but in some people that may be less efficient which could accelerate the disease," Julie Williams, PhD, from the UK Dementia Research Institute at Cardiff, who was among the researchers involved in the study, said in the joint statement issued by the research team. "The results support our growing knowledge that Alzheimer's disease is an extremely complex condition, with multiple triggers, biological pathways and cell types involved in its development. We are unmasking more of these causes year on year."

What Do the Findings Mean for Alzheimer's Treatment?

The current study is a giant leap forward in the effort to understand Alzheimer's and develop treatments that may delay or prevent onset of the disease, according to the researchers.

However, Gabriel Zada, MD, a neurosurgeon at Keck Medicine of USC, cautions that people should not look to use these findings as a way to diagnose their Alzheimer's risk. He explains that the findings are exploratory and require more research in order to fully understand how to identify, intervene, and track patients with these genetic markers.

Dr. Zada described the current findings as a stepping stone to more accurately predicting a person's genetic risk.

"An understanding of high risk or susceptibility gene signatures in certain subsets of people may provide an opportunity for earlier diagnosis and hopefully one day a mechanism to intervene and prevent or curb the mechanisms underlying Alzheimer's disease," said Dr. Zada.

By understanding the role of these genes in Alzheimer's, the study can lay the groundwork for developing gene-specific treatments and personalized medicine in the future. The next step towards finding treatments for Alzheimer's is for researchers to focus on the specific risk genes identified in the study and closely examine their role in the dysfunction and death of brain cells, according to the study.

"We don't want to just provide a list of genes. We need to give meaning to the [new] genetic information," Dr. Lambert told Health. "Our team is using the findings to determine how these genes could be involved in Alzheimer's progression. So we have both sides where we identified the genes and we will soon increase our knowledge about how these genes impact development."

While researchers continue their work, Dr. Zada says there are many things people can do today to lower their risk of developing the disease.

"We believe that focusing on general well-being, including exercise, staying mentally active, avoiding smoking and drinking, and getting solid sleep may help lower the onset of Alzheimer's disease."

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