Is Alzheimer’s written in your genes?


By Robin Brisbourne | Monday 25 July 2016

Research updates from Alzheimer’s Association International Conference 2016

This week dementia researchers from six continents, hundreds of research institutions and countless different backgrounds have made their way to Toronto for the world’s largest meeting of dementia researchers – the Alzheimer’s Association International Conference 2016. Clinicians and pharmacologists will rub shoulders with cell biologists and geneticists as they share their latest findings, forge new partnerships and drive progress towards their common goal to unravel the complex causes of dementia and find new ways to help people living with the condition.

Yesterday was the first day of AAIC 2016 and the conference featured a number of sessions about Alzheimer’s genetics and the progress being made in this important field. Much of our current understanding of Alzheimer’s comes from genetic studies that have provided a direction for other types of research and are the first step on the path to new treatments. People are also interested in genetic research because it can help us make sense of our own risk of the disease and the role that family history of Alzheimer’s can play.


Rare faulty genes

There are very rare faulty genes, or ‘mutations’ in three genes that can directly cause Alzheimer’s disease. As these genes are passed down in families (around 500 of them globally), we call this familial Alzheimer’s disease. There is a 50% (1 in 2) chance that a parent with one of these mutations will pass the faulty gene on to one of their children. People who inherit one of these faulty genes will go on to develop Alzheimer’s during their lifetime – often in their thirties, forties or fifties.


In the late 80’s and early 90’s scientists identified these genes and found that they affect the amount of a protein called amyloid in the brain. These genetic breakthroughs set scientists on a path of discovery and underpin much of our current understanding of the disease. Now, 25 years later, researchers are trialling drugs that target biological processes first highlighted by this genetic work. While most researchers think that there are no more of these Alzheimer’s-causing genes to find, Alzheimer’s geneticists aren’t hanging up their lab coats just yet.


Less than one percent of cases of Alzheimer’s disease are familial. In fact, the vast majority of people with Alzheimer’s do not have a genetic mutation that directly causes the disease. They have what is known as ‘sporadic Alzheimer’s disease’. It’s not entirely clear why some people develop sporadic Alzheimer’s while others don’t, but a person’s risk genes – along with age and a number of lifestyle factors – still play an important role. These genes do not cause Alzheimer’s but they make someone more or less susceptible to developing it.

Thanks to your donations, Alzheimer’s Research UK-funded scientists have so far identified over 20 risk genes for sporadic Alzheimer’s disease. Each of these genetic discoveries tells us something important about Alzheimer’s and opens up a new avenue for research. Scientists believe there are more of these risk genes to find but, because our genetic code is so enormously complex (encoding over 20,000 different genes), it is difficult to track down every gene that might be playing a role, especially if they only exert a relatively small influence on our risk.

Current research

Yesterday we heard from researchers working hard to pin down some of these, as yet undiscovered, risk genes. The Alzheimer Disease Sequencing Project (ADSP) is a US initiative aiming to use the latest technology to identify some of these genes. Interestingly, researchers working on this project have linked two new genes called OPRL1 and GAS2L2 to Alzheimer’s risk. The team is now running a follow-up study to try and confirm this promising finding. Like previous genetic discoveries, unpicking what these genes do inside cells, could reveal new processes driving Alzheimer’s that we never knew about before. These discoveries can transform how we study the disease and focus the search for new treatments.

But the genetics of Alzheimer’s isn’t all bad news. Genetic risk cuts both ways and just as some genes are linked to an increased risk of Alzheimer’s, some also reduce our risk. The best known and most influential Alzheimer’s risk gene is called APOE4. There are three different versions of the APOE gene – APOE2, APOE3 and APOE4. We inherit two copies, one from each parent.

People who have one copy of APOE4 (about 25% us) are around three times more likely to be affected by Alzheimer’s and people who have two copies of APOE4 (around 2% of people) are thought to be more than eight times more likely to develop Alzheimer’s.

Despite this greatly increased risk, some people with two copies of APOE4 don’t go on to develop Alzheimer’s. Researchers believe that some of these people may have protective genes that are counteracting the harmful effect of APOE4.

We heard from a researcher from New York who has been analysing the DNA of older people with the APOE4 gene. The US team identified versions of genes that were more common in APOE carriers who haven’t developed Alzheimer’s compared to those with symptoms of the disease, suggesting those genes could drive resilience to the disease. The researchers are planning to build on these indications and analyse the genetic code of more people with the APOE4 risk gene to test their findings. Discovering which biological processes these protective genes control will help scientists to better understand Alzheimer’s risk and could yield new targets for future treatments to counteract the disease.

A person’s risk of Alzheimer’s is influenced by age, genetics and lifestyle factors and it’s vital that we start to unpick the complex interplay between these risk factors. Discovering genes that could protect against diseases like Alzheimer’s helps point researchers towards targets for new drugs.

Dr Rosa Sancho, Head of Research

You can find out more about the role of our genes in dementia on our website. We’ll be keeping you up-to-date with the conference throughout the week here on the blog.

Read more about our current genetic research projects and donate to support pioneering studies like these:

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About the author

Robin Brisbourne

Team: Science news