'I know I'll get Alzheimer's... but when?' One woman's story of how a DNA test changed the course of her life for ever

 APOE is the most powerful risk gene for Alzheimer’s disease that we know. One variant – APOE2 – reduces your risk slightly while APOE4 raises itAbout one in five of us carries one copy of APOE4, which probably brings a three times greater risk of developing Alzheimer’s disease – typically late onset – but carriers could still live to a ripe old age without ever getting it. If you have two copies of APOE4, which is much less common (just one in 50 of us has two copies), you have nine to 12 times the average risk, and are likely to get Alzheimer’s if you live a long life. It’s also important to say that you can get Alzheimer’s disease without carrying any copies of APOE4.As well as ‘risk genes’, there are genes where a mutation (fault) is causative – amyloid precursor protein and presenilin 1 and 2. These rare mutations will always give you the disease, typically in your 40s, 50s or 60s. They appear in families with a strong history of early onset Alzheimer’s.There is NHS testing for people over 18 with a familial faulty gene. This is preceded by counselling and many people decide not to have the test.APOE4 raises risk of late onset disease. The NHS doesn’t test for it. It’s not yet entirely clear that interventions will alter the risk of developing dementia. But there are changes we can make to reduce it: not smoking, looking after blood pressure and cholesterol, seeing friends and family and looking after our wellbeing. These are a good idea in any case.

When Gemma Stoyle’s DNA results arrived in her inbox, she was sitting in her empty classroom, waiting for pupils to file in for her next lesson. She knew it was a bad time to open it but couldn’t wait. She clicked on the link which took her to her Comprehensive Health Report and scrolled past all the weight, height, diet and exercise analysis, past her ‘fat sensitivity’ and ‘sugar metabolism’, until she found what she was looking for on page six.

It was just a few lines but marked in red, and it told her that she had two copies of the APOE4 gene – she was APOE4/4 (meaning both her parents are APOE4). Though the report didn’t give much information on what this meant, Stoyle already knew.

She knew that only about two per cent of the world’s population are APOE4/4 and it makes you nine to 12 times more likely to develop Alzheimer’s disease. In fact, a recent study has found that virtually everyone who is APOE4/4 is likely to develop the disease.

‘Looking at that email was devastating,’ says Stoyle, who was 44 at the time. ‘I was just so shocked, I felt sick. I kept rereading it, because I couldn’t believe it.’

Back then, in 2017, even fewer of us had heard of APOE4. Awareness has grown since, making headlines when Marvel star Chris Hemsworth discovered that he is APOE4/4. (He has since said that it has led him to simplify his life and spend more time with his family.)

Where once DNA testing was limited to those who’d been diagnosed with a serious genetic disease, millions of us have now sent off a swab of saliva in the post, sometimes for health reasons, more often to discover our ancestry with a company that offers health analysis as an extra. But are we prepared for what we may learn?

Gemma Stoyle was 44 when she took the gene test

Stoyle, 51, a teacher who lives in Devon with her husband and two teenage children, had taken the test largely for her sister.

‘She’d had a DNA health test to help her devise her optimum diet and exercise plan, and discovered that she had one copy of APOE4,’ she says. Having one copy gives you a three times greater risk of developing Alzheimer’s relative to the average population.

‘She set up a WhatsApp group for me and my cousins saying that we should get tested. It was almost like she needed someone to do it as she was scared and didn’t want to be the only one. The cousins didn’t want to, but as I was her older sister, I told her I would do it.’

Everyone inherits two copies of the APOE gene – one from each parent. There are three possible variants – APOE2, APOE3 (which is by far the most common) and APOE4, which is the one that carries the greatest risk of Alzheimer’s.

As Stoyle learned more, she wasn’t surprised that her sister had inherited one copy of APOE4 and assumed it was from their mother’s side. ‘My maternal grandmother had Alzheimer’s and there was also talk of a Great Aunt Betty, who went totally mad,’ says Stoyle.

At the time of her sister’s DNA test, their own mother was also struggling, though never diagnosed. ‘It wasn’t a clear picture,’ says Stoyle. ‘She was in her late 60s and had been collapsing a lot because of a car accident she’d had many years earlier which damaged her neck. She had an operation to fuse the vertebrae, but after waking from the general anaesthetic, she never regained full cognitive function. She went to a respite care home and was declining really fast.’

However, their father’s side of the family had no known history of the disease, so Stoyle certainly didn’t expect to inherit a copy of APOE4 from him too. ‘His parents died in their 80s of lung cancer. My dad is 87 and still well,’ she says.

‘The first few weeks after getting my result were horrendous,’ says Stoyle. At the time, she and her family were living in Alicante, Spain, where she was head of English for a British school. ‘My children were ten and 13, and I remember looking at them, thinking,

“I need to get a living will together. I don’t want them to have to look after me.” I didn’t want them to see me crying, so I’d go on walks where I’d sob and fret. How long had I got? I felt my mortality so sharply. It’s such a weird, lonely feeling. You’ve found this life-changing information about yourself and your possible future, but everything is still the same and almost no one understands what you’re talking about if you try to tell them – so I hardly told anyone.’

Stoyle’s husband was so worried for his wife that he contacted the Alzheimer’s Society, who provided them with lots of information on reducing dementia risk. Stoyle also dived into her own research. ‘I was obsessive,’ she says.

‘I bought books, I went online. You find recommendations around lifestyle and I did all of them immediately, nothing gradual. I started running – madly – lost more weight than I needed to lose and cut so much from my diet. I’d always been low carb, but I completely cut out sugar, alcohol, gluten and dairy.

‘I remember us having a birthday party for our daughter. All the parents were invited too, so we had a big bucket of ice with beers in it, cakes, party food. By then, I hadn’t had any alcohol or sugar for a month and I watched everyone having a good time and felt like I was living in a different reality where I couldn’t enjoy life or return to the world I’d lived in before. You can’t unknow this.’

Seven years on, and now back in the UK, Stoyle feels differently. A second test with a bigger company confirmed her APOE4/4 status. One key step for her was finding the forum APOE4.info, which was founded by someone who had stumbled across her APOE4/4 status in the same way Stoyle had.

Since there’s no medical consensus on prevention strategies for people who are APOE4/4, the site has become a space where thousands of people can compare notes and share research. ‘Finding them was a godsend,’ says Stoyle. ‘Lots of people were much older than me and still absolutely fine.’

She didn’t have counselling. ‘Most counsellors wouldn’t understand – unless it was a genetic specialist.’ She did ask her GP for a brain scan to see if there was evidence of Alzheimer’s disease already.

‘I offered to pay,’ she says. ‘The doctor didn’t seem to know what APOE4/4 was, and when I explained, she asked, “But what would you do with the results? What difference would it make?” And I suppose it wouldn’t make a difference. I’m just doing what I can to look after myself.’

Stoyle’s new diet and health regime has become part of her life. ‘I eat lots of fish, eggs, nuts, vegetables and fermented foods,’ she says. ‘I walk loads and have a treadmill at home. I try not to get too stressed and I prioritise sleep.’ Her children have not expressed any interest in knowing their own APOE status. ‘By the time they reach my age, there might be targeted treatments,’ says Stoyle.

‘They know about me but they’re young, they feel invincible and I’m not going to ruin it for them. I had fun in my 20s, I partied and I’m glad I did – I wouldn’t want anything different for them.’

Her husband wishes she’d never taken the test. ‘He saw how unhappy it made me,’ she says, ‘and I’m probably less fun now. We went to see Kula Shaker recently in Bristol. We saw them live in 1996 in Madrid and I remember drinking pints and jumping around. This time, I was drinking sparkling water.’

Stoyle’s mother died at 70 while she was still in Spain. ‘My mum had a stressful life.Her marriage ended when I was young, she had the car accident, the operation, her diet wasn’t good.

I don’t think it’s inevitable that I’ll get Alzheimer’s but I’ve accepted the fact that I might. I’m just hoping it’s in my 80s and not my 60s. I’m probably getting more fearful as I get older, watching every step. If I can’t remember a word for something, I worry that it’s the beginning.’

Somehow, though, she feels lucky. ‘I’m glad I’ve had time to take preventive steps. I’m also determined to travel more. I’d love to study again, to see and learn more things while I can. It’s made me want so much for the children too – I want them to enjoy their lives and pack lots in. In a way, I feel more grateful. While some people say, “Oh no! Another birthday!”, I’m counting my blessings.

‘I absolutely don’t regret knowing that I’m APOE4/4,’ she adds, ‘but there are a lot of companies that will take your money, pass on the information and leave you to it. Anyone taking a test needs to be prepared for what they might find and probably think about it a lot more than I did.’

Should I get tested for APOE4? 

By Nick Fox, professor of clinical neurology and director of the UCL Dementia Research Centre

•  APOE is the most powerful risk gene for Alzheimer’s disease that we know. One variant – APOE2 – reduces your risk slightly while APOE4 raises it
• About one in five of us carries one copy of APOE4, which probably brings a three times greater risk of developing Alzheimer’s disease – typically late onset – but carriers could still live to a ripe old age without ever getting it. If you have two copies of APOE4, which is much less common (just one in 50 of us has two copies), you have nine to 12 times the average risk, and are likely to get Alzheimer’s if you live a long life. It’s also important to say that you can get Alzheimer’s disease without carrying any copies of APOE4.
• As well as ‘risk genes’, there are genes where a mutation (fault) is causative – amyloid precursor protein and presenilin 1 and 2. These rare mutations will always give you the disease, typically in your 40s, 50s or 60s. They appear in families with a strong history of early onset Alzheimer’s.
• There is NHS testing for people over 18 with a familial faulty gene. This is preceded by counselling and many people decide not to have the test.
• APOE4 raises risk of late onset disease. The NHS doesn’t test for it. It’s not yet entirely clear that interventions will alter the risk of developing dementia. But there are changes we can make to reduce it: not smoking, looking after blood pressure and cholesterol, seeing friends and family and looking after our wellbeing. These are a good idea in any case.

For more information, call the Dementia Research Infoline on 0300 111 5 111