Biotechnology Lead Wendy Nelson on coexistence with ApoE4, the Alzheimer’s disease gene

Written by Katie Cobb | January 20, 2023

Through a 23andMe test, Wendy Nelson, PhD, discovered that she carried two copies of the Alzheimer’s disease biomarker ApoE4 – the “Alzheimer’s gene”. It has changed the way she thinks about brain health.

When Wendy Nelson, Ph. D., discovered she carried two copies of the Alzheimer’s disease biomarker ApoE4, a genetic variant associated with an increased risk of Alzheimer’s disease, she drew on her career in biotechnology to figure out what to do next.

When Nelson was older, her grandfather and mother had Alzheimer’s disease, as did her maternal aunt.

“So, my mom was always very afraid of getting Alzheimer’s, and she definitely had it when she was very young,” she said, “Being patient.” In fact, Nelson’s mother was diagnosed with Alzheimer’s disease in her mid-60s, and Nelson remembers seeing signs of Alzheimer’s symptoms before that.

This was her mother’s side of the family – but what about her father’s side? After her mother dies of Alzheimer’s disease in 2022, Nelson decides to pursue genetic testing. She was curious as to whether she carried any of the genetic biomarkers for Alzheimer’s disease.

There are dozens of genes that have been linked to an increased risk of Alzheimer’s disease. Some of these genes have little effect on a person’s likelihood of developing Alzheimer’s disease. Others have a lot. One specific genetic variant, called APOE4, has gained a reputation as the “Alzheimer’s gene.”

This APOE4 variant does not carry the Alzheimer’s gene. Always Get sick—but because of a deep professional background in biotechnology, Nelson felt that the more she knew about Alzheimer’s risks, the better prepared she was to make lifestyle modifications that could stave off Alzheimer’s disease or its symptoms.

No matter how prepared she was for the results, it still rocked her world. She found that not only had she inherited one copy of the APOE4 variant from her mother’s side of the family – she had also inherited one copy from her father, making her symmetric APOE4 carrier.

“I did 23andMe, as a lot of people do these days, and unfortunately, it kind of confirmed my worst fears instead of alleviating them,” she told Being Patient on LiveTalk recently. “I guess it took me a while to swallow that pill. But then, I’m a scientist, so I’m not going to sit back and accept my potential fate. I wanted to know what I could do about it.”

Learn more about how she decided to pursue genetic testing, what the process was like, how she felt when she got her results, and most importantly, what she did next. Watch the full conversation hereOr read a transcript of the conversation below:

Be patient: I have deliberately sought to understand your genetic condition. Tell us a little bit about that. What went into this decision?

Nelson: Well, I’m in the biotech industry, I have a Ph.D. in science, and I’ve been working in the biotech industry for almost 30 years now. Now, there are things you can do — there are clinical trials and stuff. Five or six years ago, I didn’t want to know because there was nothing you could do if you found you had it or were prone to getting it. They say you can eat healthy and you can exercise. I do, but so does my mom. I’ve watched the clinical trial space and I know that they’re trying to get people into clinical trials early on and that being pregnant qualifies you for some clinical trials now. So, that’s part of the reason I decided to find out, but it was also partly because I was hoping to only carry one. I was hoping it would help relieve some of the stress and fear I carried with me, and unfortunately, it backfired. I found out I was carrying two, and that was before my dad went down that road. I did 23andMe, as a lot of people do these days, and unfortunately, it kind of confirmed my worst fears instead of alleviating them.

Be patient: For people who haven’t had their genetic testing, how did you find this information on 23andMe?

Nelson: they send you a great report with all kinds of interesting information about a million other things then it has an ApoE4 variant. You say you carry ApoE4 and have a significantly increased risk of developing Alzheimer’s disease, and I’m like, “Uh, crap.” It’s as clear as day, and there’s a whole big page on it.

Be patient: Being in biotech, you are well versed in genetics, perhaps more than the average person. But, you had two copies of ApoE4, not one, and you didn’t expect that. So how did you process that information, and how did you deal with it?

Nelson: It’s very frustrating and frustrating and frustrating at first. I guess it took me a while to swallow that pill. But then, I’m a scientist, so I’m not going to sit back and accept my potential fate. I wanted to know what I could do about it. So, I did some more research on my own, on what you can do. I went on a low level of rosuvastatin to reduce my cholesterol. There are more and more links between cholesterol buildup and Alzheimer’s disease, which is known to be more beneficial for younger people. Just things like that.

I guess it took me a while to swallow that pill.
But then, I’m a scientist, so I’m not just going to sit around
Go back and accept my potential fate. I wanted to
Find out what I can do about it.”

Be patient: You mentioned clinical trials — have you joined any clinical trials for people who don’t have Alzheimer’s disease but have a genetic variant?

Nelson: I’ve got my eyes on some companies. There is a very interesting company called Alzheon. Here in the Boston area, they have excellent data on stage 2 Alzheimer’s patients for what oral pill would help in the early stages. It helps prevent oligomerization from occurring in the first place and, hopefully, prevents tau tangles and amyloid plaque buildup from occurring in the first place. They just signed up for their Phase 3 trial in patients, and the first read should be in mid-2024. If they have good solid data, they’ll open it up to carriers like me in 2025. So I’m watching companies like that have potential new things coming their way. To work. There’s also a company called Cognito Therapeutics that I’m watching in San Francisco. This is completely different – it’s like a virtual reality headset that stimulates the auditory and sensory effects of visible light. It seems to break down these build-ups in your mind. So, I’ve got my eyes set on the things I’d be more than happy to try. So, I’ll be totally involved when companies like this open up their experiences to carriers.

Be patient: Yes, we’ve already covered those two companies. I want to talk to you a little bit more about the science behind this because, as a PhD, you obviously know more than the average person. Can you tell us a little bit about what you know about ApoE4, its interaction with cholesterol, and why people with this gene variant tend to do things wrong versus someone who doesn’t have this gene?

Nelson: It’s a known biomarker, right? This is definitely a sign of a clear link between high cholesterol and Alzheimer’s disease. Therefore, no one knows the exact biology of Alzheimer’s disease, so a lot of it is speculation. But, things like the biomarker ApoE4 have been found time and time again to be an obvious link. So, this is why anything you can do to keep your cholesterol low, which is obviously cardiovascular disease as well, can only be good for you and your brain.

Be patient: Learning about brain health also means understanding how biological systems are connected. This is probably the easiest way to understand what risk factors are in your mind, right?

Nelson: Everything in the human body is connected in one way or another. You can do all the right things and still get a disease like Alzheimer’s because of a bunch of bad genetic cards you were dealt.

<< Considering genetic testing for Alzheimer's disease?
Check out our interactive Being Patient guide. >>

There are a lot of correlations and signs that things are risk factors. But even if you don’t have these risk factors, you could develop Alzheimer’s disease. And even if you have all of the risk factors, you won’t necessarily develop Alzheimer’s disease. So, there is also some genetic predisposition and luck thrown into the mix.

Be patient: Finding out whether plaque may be present in the brain is a step further than finding your genetic condition. Want to try the blood tests coming to market to find out?

Nelson: Honestly, I don’t know if I want to know yet. I haven’t done it yet because, as we all know, damage to your brain starts 15 or more years before you have symptoms. I don’t want to know if my years really counted. If I had to find out if I had to take this test to get into a clinical trial that I thought was really promising, that’s when I would find out.

Be patient: tell us a little bit about how things have changed. Are you doing things differently than you did before now that you know you have ApoE4?

Nelson: To some extent, but not more than we should all be doing anyway, and that is living each day to its greatest potential. I’ve seen my parents make the mistake of putting everything off until their retirement. You know, I’ve heard this excuse over and over again: “Oh, I’d like to go there. We’ll do that when we retire.” Then, by the time my dad retired, he’d retired to take care of my mom, so it was too late. So, I will not make this mistake. I’m just trying to do what I want to do now as time allows. I’m also trying to watch the Alzheimer’s disease space more actively and see what I can do for myself and my family. But again, we all want to live as healthy a life as possible. So, I would say it’s a little bit different, but not that much.

Be patient: what would you say to those people who are already considering genetic testing? Do you advise them to do so or not?

Nelson: It depends on their personality. Some people, if you have the mindset that it will enable you to research potential clinical trials or help yourself, then by all means, go and do it. If it’s going to sit on your shoulders and burden you for the rest of your years, stop until there’s something you know and more drugs are on the market. People should wait until they are in the right mindset and feel there is enough hope to know that there is no such burden for them and try to do something about it.

This interview has been edited for length and clarity.

Katie Cobb is a writer and theater artist based in Raleigh, NC.

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