With a 23andMe test, Wendy Nelson, Ph.D., discovered she carries two copies of Alzheimer’s genetic biomarker ApoE4 — the “Alzheimer’s gene.” It changed the way she thinks about brain health.
When Wendy Nelson, Ph.D., discovered that she carries two copies of Alzheimer’s genetic biomarker ApoE4, a gene variant associated with heightened Alzheimer’s risk, she leaned on her career in biotech to figure out what to do next.
When Nelson was growing up, her grandfather and her mother’s father had Alzheimer’s, as did her mother’s aunt.
“So, my mom was always very afraid of getting Alzheimer’s, and sure enough, she did get it and was pretty young,” she told Being Patient. Indeed, Nelson’s mother was diagnosed with Alzheimer’s in her mid-60s, and Nelson recalls having seen 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’s death of Alzheimer’s in 2022, Nelson decided to pursue genetic testing. She was curious about whether she carried any of Alzheimer’s disease’s genetic biomarkers.
There are dozens of genes that have been linked to increased Alzheimer’s risk. Some of these genes have just a tiny bit of influence over a person’s likelihood of developing Alzheimer’s; others have quite a lot. One particular gene variant, called APOE4, has accrued a reputation as “the Alzheimer’s gene.”
Carriers of this APOE4 “Alzheimer’s gene” variant don’t always develop the disease — but coming from a deep professional background in biotech, Nelson felt that the more she knows about her Alzheimer’s risk, the better equipped she might be to make lifestyle modifications that can stave off Alzheimer’s or its symptoms.
No matter how prepared she felt she was for the results, they still rocked her world. She found that not only did she inherit one copy of the APOE4 variant from her mother’s side of the family — she also inherited one from her father, making her a homozygous carrier of APOE4.
“I did 23andMe, as a lot of people are doing these days, and unfortunately, it sort of confirmed my worst fears instead of alleviating them,” she told Being Patient in a recent LiveTalk. “I think it took me a little time to swallow that pill. But then, I’m a scientist, so I’m not going to just sit back and accept my likely fate. I wanted to figure out what I can 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 here, or read a transcript from the conversation below:
Being Patient: You deliberately sought out to understand your genetic status. Tell us a little bit about that. What went into that decision?
Nelson: Well, I’m in the biotech industry, I have a Ph.D. in science, and I’ve been 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 used to not want to know because there was nothing you could do if you were found to carry it or prone to get it. They say you can eat healthily and you can exercise. I do those, but my mom did them too. I’ve watched the clinical trial space and know that they’re trying to get people onto clinical trials earlier and that being a carrier qualifies you for some clinical trials now. So, that’s part of the reason I decided to find out, but it was also partially because I was hoping I was only going to carry one. I was hoping it would help alleviate some of the stress and fear I carried with me, and unfortunately, it backfired. I found out I did carry two, and it was before my dad went down this road. I did 23andMe, as a lot of people are doing these days, and unfortunately, it sort of confirmed my worst fears instead of alleviating them.
Being Patient: For people who haven’t gotten their genetic tests, how did you find that information on 23andMe?
Nelson: They send you a nice report with all kinds of interesting information about a million other things, and then it has the ApoE4 variant. It says you carry the ApoE4 and have a significantly increased risk for Alzheimer’s, and I’m like, “Ah, crap.” It’s as clear as day, and there’s this whole big page on it.
Being Patient: Being in biotech, you’re well educated on genetics, probably more so than the average person. But, you had two copies of ApoE4, not one, and you didn’t expect that. So, how did you deal with that information, and how did you process it?
Nelson: It is very disappointing and discouraging and depressing at first. I think it took me a little time to swallow that pill. But then, I’m a scientist, so I’m not going to just sit back and accept my likely fate. I wanted to figure out what I can do about it. So, I did more research on my own, on what you can do. I have gone on low-level rosuvastatin to decrease cholesterol. There are more and more ties between cholesterol buildup and Alzheimer’s, which has been known to be more helpful for younger folks. Just things like that.
“I think it took me a little time to swallow that pill.
But then, I’m a scientist, so I’m not going to just sit
back and accept my likely fate. I wanted to
figure out what I can do about it.”
Being Patient: You mentioned clinical trials— have you joined any clinical trials for people who don’t have Alzheimer’s but have a genetic variant?
Nelson: I’ve got my eye on some companies. There’s a very exciting company called Alzheon. Here in the Boston area, they have excellent phase two data in Alzheimer’s patients for what is an oral pill that would help upstream. It helps prevent the oligomerization process from happening in the first place and, hopefully, prevent those tau tangles and amyloid plaque buildup from occurring in the first place. They have just enrolled their phase three trial in patients, and the first readout should be in mid-2024. If they have good solid data, they will open it up to carriers like me in 2025. So, I’ve got my eye on watching companies like that that have possible new things coming down the pipeline. There’s also a company called Cognito Therapeutics that I’m watching in San Francisco. This is very different— it’s almost like a virtual reality headset that does hearing stimulation and visual light sensory effects. It’s apparently breaking down these buildups in your brain. So, I’ve got my eye on things I would be happy to try. So, I will absolutely join when companies like that open up their trials to carriers.
Being Patient: Yes, we’ve actually covered both of these companies. I want to talk to you a little more about the science behind this because, as a Ph.D., you obviously know more than the average person. Could you tell us a little about what you know about ApoE4, its interaction with cholesterol, and why people with that genetic variant are predisposed to things going wrong versus someone without that gene?
Nelson: It’s a known biomarker, right? So that’s a signal that for sure there’s a clear tie between high cholesterol and Alzheimer’s. So, no one exactly knows the biology of Alzheimer’s, so a lot of it is speculation. But, things like the ApoE4 biomarker have been found over and over again to be a clear tie. So, that’s why anything you can do to keep your cholesterol down, which is obviously a cardiovascular thing as well, can only be good for you and your brain.
Being Patient: Learning about brain health also means understanding how biological systems relate. That is probably the easiest way to understand in your mind what the risk factors are, right?
Nelson: Everything in the human body is connected in some way or another. You can do all the right things and still get a disease like Alzheimer’s because of a bad genetic set of cards that was dealt to you.
There are lots of relationships and indications that things are risk factors. But even if you don’t have those risk factors, you can get Alzheimer’s. And even if you have all the risk factors, you don’t necessarily get Alzheimer’s. So, there’s also some genetic predisposition and luck that gets thrown into the mix.
Being Patient: Finding out that potentially having plaque in the brain is one step further than finding your genetic status. Do you want to try the blood tests coming to market to find out?
Nelson: Honestly, I don’t know if I want to find out yet. I have not as of now because, as we all know, the damage to your brain starts 15 years or more before you’re symptomatic. I don’t want to know if my years are already being counted. If I had to find out if I had to get that test to enter a clinical trial that I thought really showed promise, that’s when I will find out.
Being Patient: Tell us a little bit about how things have changed. Are you doing things differently than you were before now that you know you have ApoE4?
Nelson: Somewhat, but not more than what we all should be doing anyway, and that’s living every day to its greatest potential. I saw my parents make the mistake of putting everything off until they were retired. You know, I heard that excuse over and over again: “Oh, I would love to go there. We’ll do it when we’re retired.” Then, by the time my dad retired, he retired to take care of my mom, so it was too late. So, I’m not going to make that mistake. I’m just trying to do whatever I want to do now as time permits. I’m also trying to actively watch the Alzheimer’s space more and see what I can do for myself and my family. But again, we all want to be living as healthy lives as possible. So, I would say it’s slightly different, but not by that much.
Being Patient: What would you say to those people who are actually considering genetic testing? Would you recommend they do it or not?
Nelson: It depends on their personality. Some people, if you have the mindset that it will empower you to look for potential clinical trials or help for yourself, then by all means, go do it. If it’s going to sit on your shoulders and weigh you down the rest of your years, hold off until there’s something you know and more drugs are available on the market. People should wait until they’re in the right mindset and they feel there’s enough hope out there for them to know that to not have this burden on them and try to do something about it.
This interview has been edited for length and clarity.
Katy Koop is a writer and theatre artist based in Raleigh, NC.