Steve and Virginia are joined by Lindsay Hohsfield, PhD, a neuroscientist at UCI and co-founder of a non-profit organization called Youngtimers, to discuss the role that our genes play in Alzheimer’s disease. She helps the audience understand the difference between sporadic and familial Alzheimer’s, early- versus late-onset Alzheimer’s disease, and gives advice to those who are concerned about their genetic risk of developing the disease.
To learn more about Lindsays organization, Youngtimers, please visit https://www.youngtimers.org
From the University of California, Irvine, this is UCI MINDs, spotlight on care, the podcast where we share stories, experiences, tips, and advice on caring for loved ones affected by Alzheimer's and other dementias.
Hello, and welcome to another episode of spotlight on care. Today we're going to be talking about I think, one of the questions or one of the topics that many people have some information about, but not necessarily a lot of clarity, which is what's the, you know, genetic connection between Alzheimer's and and the disease of Alzheimer's and how prevalent it is. And if I have someone in my family, am I going to get it all of those kinds of things are swimming out there. And we have a young lady Lindsay Hohsfield, who's going to shed some light on that our topic is going to be questions about the genetics of Alzheimer's, Virginia, is there anything that you would like to start off with your experience with this issue?
I'm glad Lindsay is here to explain a lot of these things to us. Of course, I speak for many people out there who have a parent who experienced Alzheimer's. And it's always in the back of our minds, uh oh, how much of this is going to land on me? You watch the suffering that your parent goes through. And it was always in my mind, I didn't dive into it heavily. And I'm happy that you're here to explain it to us in layman's terms. You know, what are the chances? How much do we have to be worried about or concerned as caregivers?
Yeah. And the only note that I like to add is my own experience with my own children, who their grandmother had was senile. We don't know whether she had Alzheimer's on my wife, Paty, as you all know, had it and the experience they had with the thought process that they could possibly be a candidate for it. And it's been interesting over the years since Paty was diagnosed, to see them getting more and more open to the idea of information and knowledge. And I think that's what we'll accomplish today. So let me welcome Lindsay. Wish you could all see her she's just as bright star in our, in our lives. So a little bit on Lindsay herself. First of all, she's a doctor, PhD assistant project scientist working here at UCI. Lindsay has her PhD in neuroscience. And her research interests focus on understanding how amyloid plaques accumulate in Alzheimer's disease brain and how we can develop methods to use our own immune system to clear this toxic peptide from the brain. Even of more interest probably, besides her own research is that Lindsay is an entrepreneur. She has started co founded at an organization called Young timers, a nonprofit organization that seeks to promote community education support and research for individuals and families affected by early onset and the key word here, familial Alzheimer's disease. And we'll expand a little bit on that with our questions. Again, welcome, Lindsay.
Thank you for having me.
Give us a little background on why you dedicated yourself to research on Alzheimer's.
Yeah, I mean, like both of you, I had it in the family. So it was actually shortly after I graduated from high school, my father was diagnosed with Alzheimer's disease, he was 48 years old at the time. And to this day, I can still remember sitting at the kitchen table, and my mom saying the words your Dad has Alzheimer's. I think in the beginning, you know, it's kind of shock and disbelief. And then, you know, this new reality kind of sets in you can't avoid it. And yeah, after that, your your life is just never the same. You're never the same. And I think for me, there was never this option to to ignore it, to sit in that pain, and just wait for the disease to take hold of my dad. So the next day I went to the library, I went and checked out every book on Alzheimer's disease. I read every book on Alzheimer's disease that I could get my hands on a year or two into college, I was studying molecular and cellular biology, and I realized that there's just so much that we don't know about the brain. And there's so little we know about Alzheimer's disease and instead of just waiting to read about potential cures, I decided that I didn't want to sit on the sidelines and I asked an Alzheimer's researcher on campus to join his lab. And that was almost 17-18 years ago and I've been dedicated my life to research ever since.
That's a great statement. I can't imagine what it's like to know your parent at that age has got the disease. So let's start with the big one right off the bat. What is early onset Alzheimer's? And what age range does that occur?
early onset Alzheimer's is defined as someone who has or is diagnosed with Alzheimer's disease before the age of 65. So if someone starts showing Alzheimer's related dementia or symptoms, so this could be they have a hard time creating new memories. They're confused or disoriented. They might have difficulty with language or numbers or problem solving any of that. They show any of those symptoms before the age of 65, than they would be considered or diagnosed with early onset Alzheimer's disease. And just a little bit of background studies have shown that about 10% of Alzheimer's cases are early onset cases. So the majority of Alzheimer's disease that we do hear about, you know, in the news and such occurs in people who are diagnosed after the age of 65, which we call late onset Alzheimer's disease. So that's the difference before 65 is early onset after 65 is late onset.
Okay, so so let's get to this question about genetic connection that exists about Alzheimer's. Would you please explain the basic differences between sporadic and genetic Alzheimer's?
Sure. So as you highlighted in your question, there are two different types of Alzheimer's disease that clinicians and researchers define as sporadic and then you have genetic, which we know a lot of us, but it's better known as familial Alzheimers disease. And these two different types of Alzheimer's disease refer to what is causing the disease. And this is different than when somebody sees symptoms. So that's very different than early versus late. So when we spoke about early versus late, again, it refers to when the disease began, but it doesn't clarify for us whether there's a genetic component at all. And for most Alzheimer's cases, we still don't know the cause of disease. Researchers predict there's a combination of factors such as environment and lifestyle and that sort of thing. However, there is a small proportion of Alzheimers patients where we actually do know the cause of the disease. And these are rare mutations. For anybody who's not familiar what a mutation is, it's basically a genetic change in your, your DNA code or your blueprint. And these mutations occur in one of three genes. We call them app, presenilin one and presenilin two, for anybody who's interested in in that,
and that's as far as we're gonna go. Right?
Exactly. And so people who carry these very rare mutations, they, they likely are they they did inherit this mutation from a parent, which means that they had inherited from their parent and so on. So people with this type of Alzheimer's disease, again, we often refer to as familial Alzheimers disease, because it's hereditary. Because it runs in the family, people with these rare mutations usually see family members with Alzheimer's disease in in at least three generations. So that means they saw it in their parent, they saw it in their grandparent, and there's maybe even a great grandparent, they usually have, you know, lots of aunts and cousins who have it, this is very different than somebody who just sees it in one member of their family.
So let's just follow up on that for a second. So familial, or genetic, we prefer the word familial, because it really describes why right, and sporadic which appeals to the vast majority of people. So you said small percentage, what kind of percentages are we talking about?
less than 1% of all Alzheimer's disease cases are these very rare, early onset familial form of Alzheimer's disease
One copy, you get one from one parent, right. And that gives you the condition as opposed to having to get one from each parent?
this type of mutation or disease is called autosomal dominant to put in more simple terms, you know how, with eye color brown, if you have, you know, a parent with brown and blue, you know, you often end up with a child with brown because brown kind of is dominant over blue. So in this case, this this mutation is dominant. And so yes, you would only need to inherit one from that parent and you would get the disease but again, because of that, you really only have a 50% chance of inheriting the disease because, you know, there is the potential that you don't inherit, your parent has two alleles, right? These are two copies. So one One of them has the disease carrying mutation, and the other one doesn't, right? So you've a 50% chance that you'll get, you know, the diseased one, I think just just to clarify to what makes this familial form different is that it usually can, like occurs in people at a significantly younger age. So the average age of onset in this group is usually 40s, somebody in their 40s. And again, I just want to clarify that this type of Alzheimer's is fully explained by genetics. If you do inherit one of these mutations, there is a 99.9 chance that you will develop the disease. Although this is a very rare population, I just want to say it's really important population, because we've learned a lot about how the disease progresses. In these patients. Researchers actually have have, like, They predict that, you know, there's multiple factors that contribute to sporadic Alzheimer's disease, and that they converge to cause the disease. Some of these factors might be genetic. So I think that's where people maybe get tripped up. Is that Well, okay, there is my my aunt had it, or my parent had it, this must be genetic. But it's very different than this very rare form. I think it's important to clarify that in sporadic we don't know the cause, we think that there might be a genetic component to it. Okay. With familial Alzheimer’s disease, we know the cause. And we know that it's basically genetic. And I think for anybody listening who's at risk, let's say because they maybe have a loved one who who had Alzheimer's disease is just worried about it. Researchers have identified more than 20 potential genetic factors that may be associated with an increased risk or susceptibility of this sporadic late onset form of Alzheimers disease, including APOE. So to answer your question, just wrapping it all up. We know the genetic connection to familial Alzheimer's disease. And we know that there are certain genetic risk factors that increase a person's risk for sporadic Alzheimer's disease. But I think a complete picture of the genetic connection to sporadic Alzheimer's disease is still very much lacking today.
And that's what you're working on.
Yes, me and a lot of other other researchers. Yeah.
One of the things that we hear from people who are worried about their family connection is that they're afraid about this. And we talked a little bit about this genetic connection. And you mentioned how rare it is. What's your advice in terms of whether or not I've got multiple family members? I only have one or two, what where is this? And what's been your experience with this idea, especially with your organization, young timers?
Well, first of all, I just want to say that it's it's very understandable and normal, I think, to have this fear, you know, to watch this in a loved one or a parent. And then, you know, think about your own risk. But before I get into the details, I think it's really important to clarify, you know, what type of genetic connection correlates to the likelihood or risk that a family member will develop Alzheimer's disease. So as I mentioned earlier, there's this familial form of Alzheimers disease where the genetic connection to Alzheimer's disease is very strong, right, we already talked about if you inherit it from one parent, there's a 99.9% chance you'll get it. This type of Alzheimer's disease, I just want to reiterate it again, is it's very rare, it's in less than 1% of all Alzheimers disease cases. So for all the other cases of Alzheimer's disease, which are sporadic, researchers are still trying to tease out what these genetic connections are, and whether they exist. So one of the highest and most prevalent we talked earlier about these genetic factors that could increase your risk for Alzheimer's disease. One of them as I mentioned, is apoe or apolipoprotein E. And there are different genetic forms or alleles of this genetic factor
Sorry what's an allele.
they're just basically pieces of your DNA that are, and you have two copies of them, you get each one from your parent. So there are multiple different forms of this apoe and there's apoe 2 apoe three and apoe 4 having one or two of these apoe 4 alleles increases a person's risk of developing Alzheimer's disease. And the NIH has said that about 25% of people in the world actually carry one copy of apoe 4 and about two to 3% of people carry two copies. And I just want to state those facts, because there actually are a lot of people that have these apoe four alleles, right, that apparently increase your risk, but that doesn't translate into everybody, all of those people getting Alzheimer's disease. So apoe four is called a risk factor for a reason it increases a person's risk of developing the disease. But just because you have apoe 4 that does not mean that you will get Alzheimer's disease, there are some people with apoe 4 that never get Alzheimers disease. And then there are others without apoe 4 that do develop Alzheimer's disease. So again, it's all more statistics and risks than actual causality. And I think there's still a lot for us to learn about this genetic connection to sporadic or this non familial Alzheimer's disease. And so I think at this point, to answer your question, it's really difficult to determine the likelihood a family member has a genetic connection to a person with sporadic Alzheimer's disease,
how would you go about finding out whether or not you have a connection.
So I would say if a listener has at least three generations of Alzheimer's disease in their family, then it's probably a good idea for them to talk to either their loved ones neurologist who has Alzheimer's disease, they could also contact their local ADRC, which is an Alzheimer's disease Resource Center, which there are multiple located throughout the US. There's also another center and institute called the dominantly inherited Alzheimer's network (DIANE). And they kind of specialize in treating these patients with this very rare familial form of Alzheimer's disease. By connecting with these different, you know, professionals or professional groups, they can connect you with what I think you is your next important line of contact, which is a genetic counselor, they can help you determine if there is in fact, a genetic connection. Also, I just want to mention, if you if you do think that you fall under this category, where you have at least three generations, and you want to talk to somebody, it is recommended that the symptomatic so the person that actually has the disease be tested first. So it's important to for family members, I think, before they go to a neurologist before they contact their local ADRC. Before they contact DIANE, that they discuss, have this conversation together because a genetic connection that that means that it's a family affair, and I think it's really good and important to open up that line of communication as early as possible. I also want to mention because this is just become popular in recent years, that it's not recommended that families pursue direct to consumer testing, to learn about their genetic connection to Alzheimer's disease.
Why is that?
So there was actually a case not too long ago, it was reported, I think, in the New York Times where a man found a way to actually get all of the genetic data that they had. And he searched his own genome to see if there were any mutations. And they identified that he was actually a carrier for one of these presenilin these rare mutations. And it wasn't in his family, you know, like none of his parents had had it. He hadn't had any family members, and he was like, Oh, my gosh, what happens and this does, sometimes does happen. That mutation just happens. So he contacted a genetic counselor. I'm sure it was really devastating and really difficult process. And the genetic counselor recommended that he get, you know, testing done again through a clinician where they collect your blood and you know, there's there's a thorough process of, of checking for a mutation and it's different, the standards are different than for direct to consumer testing, because you're testing one local spot of the DNA versus the entire genome. And, you know, when you're proofreading a manuscript, you're gonna make more mistakes, if you're checking one that's 1000 pages versus, you know, 10 pages, right. And so they ended up finding out that he doesn't carry the mutation. But I think for a year or two, it was not a great journey for him. So I think, again, there are standards within the field that have been set in place for a reason by regulatory bodies for a reason. And that's why we don't, you know, researchers and clinicians don't recommend that.
Well, that's a great setup. What are some of the questions you should be asking yourself about whether or not you want to know that you have this connection?
Well, I think before we get into these questions, it's just it's really, it's a really difficult question. It's a very complex question.
I didn’t promise to make them easy
And I if I can just go back though, and just say that, you know, I think the audience out there, I mean, the majority of people are maybe at risk for sporadic Alzheimer's disease. And because the genetic connection is so nuanced and complex, there are several medical associations, including the American Association of neurology, and they do not recommend genetic testing for apoe. So when we're talking about when people are deciding to get genetic testing done or not, it's for familial Alzheimers disease. It's not for sporadic, another Medical Association, the American College of Medical Genetics and Genomics, and the National Society of Genetic Counselors. So I'm just saying it's not coming from me alone. But they say that genetic test testing for susceptibility of apoe is not clinically recommended, due to its limited clinical utility and poor predictive value. So again, just to reiterate, apoe is not useful in predicting whether somebody will develop Alzheimer's disease,
I don't mean to stop, yeah, I know you're on a roll here. But um, so basically, we talk about this process. So unless you see this familial connection, which means several members, at least three, really, there's no value in doing genetic testing, until unless you're in that type of type of circumstance.
However, I do know that when you do have a loved one that has Alzheimers disease, you know, you kind of do want to learn more, you want to inform yourself and be knowledgeable. And I would say to families who are interested in learning about whether there is a potential underlying genetic cause or risk in their family, that I would recommend that they contact a genetic counselor and discuss, you know, this the risks that this disease runs in their family for their particular situation. And for their particular family, you know, maybe it is a little bit more nuanced. Maybe they have one generation, but a lot of people in that generation have it, I think it's worth, if there are those questions, it doesn't hurt to at least talk to a genetic counselor who who can walk you through that.
They may be concerned because in one generation, there are several? The affected with Alzheimer's, but not three generation, which would be a real red, red red
Red flag. Exactly. So now to get back to your question on whether you know, what you should ask yourself and whether or not you should get genetic testing again. And to clarify, this is for people who have this familial Alzheimer's disease, I would encourage them to spend a lot of time working through these questions before coming to a decision. You know, I talked to a lot of people who have this disease or who are at risk for this disease, through young timers. And one person said, you know, you can never unknow this result, you know, that I am, you know, I have a 99.9% chance of getting Alzheimer's, you know, and in our case, you can usually predict within three years of age of onset, so they not only know that they're going to get it, but they know around what age they're going to get it. This is this might be too much for somebody. So I think questions to ask yourself are, you know, what is my reason for wanting to pursue genetic testing? Am I doing it because it'll be helpful in informing other life decisions? Or am I doing it because I'm feeling pressured to do it? Think what type of personality do I have? Am I a planner? Would finding out this information feel empowering? Or would it feel like a burden? Do I have a history of psychological issues? You know, genetic counselors have said that people with a history of depression or anxiety should not undergo genetic testing. Another question is, is anyone as anybody influencing my decision? So do you feel like a parent or brother or sister or a family member? Because that really, they've studies have shown that when a person is pressured, you know, there's a lot of suicidal ideation that happens. And again, have I put a lot of work and time into this decision. So this is not a decision that I would make in in a month, I would spend a few months making that decision. I know people who have spent years, you know, trying to make this decision, and then have I come to terms with the outcome, no matter the results. So what if I test positive? What if I test negative? How will my life look? What will I do differently? Do I have an adequate support system? You know, do I have close friends that I can trust, it might be sometimes difficult to talk about this with family, because it's not only your risk, it's also their risk. So I think really finding a good network before you undergo this process is really important. And then have I found a genetic counselor or clinician that I trust that I can go to?
Well, I think you can have a great segue there into a discussion about young timers. If that is, if I have or if I know that I have this particular genetic connection. What is the value of young timers? And why did you start it?
I think there are a lot of really great Alzheimers disease nonprofits out there. But in connecting with this community, I realized that there was a huge gap in the support and resources, not only when it comes to genetic testing, but to a lot of other things that come into play when a person has a diagnosis of familial Alzheimer's disease. And like I said, it, they're usually significantly younger. So I started young timers, because I just felt like the resources and support were lacking. So if we can provide more education and resources, then people might be better equipped to come and make these decisions. And I feel like, you know, there's a lot of things that come into play when somebody is at risk, as at such a high risk genetically, there are questions about what kind of career I'm going to pursue. There's questions about, you know, how, and if I start a family, you know, when do I retire? How do I save for retirement? And also, how do I, you know, deal with a parent at a when I'm at a young age, and I potentially might have to do some caregiving as well? How do I take care of them? I mean, there's so many different things that come into play when somebody has an gets Alzheimer's disease at an early age, that it's hard to even get into. But what I found is a lot of people said, you know, there are support groups out there, but I'm the youngest person by 30 years,
kind of hard to connect when you're talking to somebody who's that different in age
very hard. And now, you know, I get emails from people who are like, Finally somebody gets it,
Why don’t you spend a second and talk about some of the services of young times. I know, we're talking about a small percentage of the population. But I think that this is the kind of thing that makes you unique and makes you know, the whole idea of finding unserved populations that need help. And that's what you're doing.
First of all, we have we provide education about this disease and awareness. We have, I think, a really great website that that walks people through, you know, like your question about alleles, you kind of have to know what that is when you when you have a genetic disease. So I think we have a lot of really good information on our website for people to learn about this disease. We've also created guides on you know, genetic testing, answering these exact questions like What Does it even look like? Genetic testing and what it what should I do before I get genetic testing done? So for example, a lot of like life insurance, or long term care insurance companies will ask if you've talked to a genetic counselor, if you're looking for a policy. And so of course, knowing getting the Insight information from people in your community can be really helpful in guiding you and these different things. And so we have there are our education there. We also offer support groups. So these are virtual support groups. We have people located throughout the US, actually even globally, and they meet once a month. And we have three support groups at the moment. One is for at risk. So people who are at risk of inheriting one of these rare mutations. Some of them already know that they carry a mutation. Some of them don't know. These people are not symptomatic. So there they could be 20 years they could be five years from their age of onset when their parent got sick. We also have a caregiver support group. So a lot of these caregivers are spouses, and some of them have really young childrenAnd I think we have one woman who has a one year old and a four year old, and a six year old and is also her husband just got diagnosed. We also have, you know, a couple people who you know, took care of their husband or wife and are now taking care of their children who are sick. And then we also have a support group for people who are symptomatic. So these are people who have already been diagnosed, and want to talk to people about what it's like to slowly, you know, get this disease, what they're going through, and we want to start more support groups. We want to start like a teens and young adults group. And then we also have been partnering with some research institutions, which is really great. So researchers have really supported our efforts.
And why is that? Because this is an important point about why you did this. And I want to make sure we have time for one more question.
So the ability to predict when somebody gets Alzheimer's is very valuable to researchers. So you have a lot of different, you know, pharmaceutical companies and research institutes developing these therapies that are trying to, you know, target Alzheimer's, disease pathologies or Alzheimer's disease and stop it or prevent it from happening. And what we found out is that once a person is already diagnosed with Alzheimer's disease, there's a lot of brain damage, there's a lot of lost brain cells, and you can't really recover from that. And so treating somebody giving somebody a drug when they already have Alzheimer's, it's probably maybe not going to do that have a huge impact. But if you have a person where you know, okay, you know, they still have their brains cells still functioning well, but maybe they have these amyloid plaques accumulating in their brain, we've actually know that they started accumulating 20 years before somebody gets sick. So if you had a therapy that, let's say, targeted these amyloid plaques, and you could give these to patients who are healthy 20 years before the disease, I mean, that's a really powerful tool that you have at hand, I think this population is the key to finding an Alzheimer's disease cure.
When you mentioned this population, what are you referring to
this rare familial Alzheimer's disease population. So these people with mutations, we can test them, and they are they're aware or not aware of their genetic status, whether they carry the mutation, and then we can give them potential disease modifying therapies, you know, again, years and years before the disease even sets in. And we've actually already, DIANE has already done this. And they've shown that some of these antibodies against amyloid actually do make a difference. And they do get rid of plaques. So I think we're really at the cusp of in a really exciting time for Alzheimer's disease. And, and I also want to just plug as well, there was a woman in Colombia who had one of these rare mutations. And she didn't get sick didn't get Alzheimer's.
Yeah. Presenilin One
Yes. Yeah. And so normally, her family members would get sick in their 40s or 50s. She never did, you know, she died in her 70s of I don't even think she had dementia. But anyway, studying her genetics are really interesting to research because basically, something in there stopped Alzheimer's disease from happening. And what's really interesting is her brain was actually filled with amyloid plaques, but they didn't have tau. So those are the main hallmarks, the main pathologies, the main things that that accumulate in the Alzheimer's disease, brain disease, amyloid plaques, and these neurofibrillary tangles, she had tons of plaques, but she had no tangles. And so now the question is why? And again, if she didn't exist, we wouldn't have this secret, you know, to uncover. And so again, that's why I think in the past, this community has really struggled, because as you can imagine, if your family is hit generation after generation by Alzheimer's disease, do they ever have a chance to recover financially, emotionally? No. And up until now, there was no organization that was dedicated to providing support and resources to these to this community?
Well, Lindsay, I think that's the reason you have such a passion for that. In one fell swoop, you just discussed why you do what you do, which is these people aren't getting the kind of support and care and understanding and the and, identifying the value that they represent to the total of research. I just want to say thank you. The information here was so valuable. So thank you, young lady, so much.
Thank you so much for joining us today.
Thank you so much for having me. And thank you for what you guys are doing.
Those of you who are interested in more information about young timers and the fabulous job that Lindsay is doing, it will be in the show notes. We will have the website address there, but it's a pretty easy name to follow which youngtimers.org. Thanks again for listening in and we appreciate your assistance.
Spotlight on care is produced by the University of California Irvine, Institute for memory impairments and neurological disorders. UCI MIND. Interviews focused on personal caregiving journeys, and may not represent the views of UCI MIND. individuals concerned about cognitive disorders, prevention, or treatment should seek expert diagnosis and care. Please subscribe to the spotlight on care podcast wherever you listen. For more information, visit mind.uci.edu