Researchers in Arizona may have found a new type of Alzheimer’s disease related to gut health

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New research is drawing a connection between gut health and Alzheimer’s disease. Scientists at Arizona State University and Banner Alzheimer’s Institute have found what they believe is a new subtype of the disease, which is linked to a lingering infection from a common virus. And, they think this could affect up to nearly half of all people with Alzheimer’s.

Ben Readhead, faculty at the ASU-Banner Neurodegenerative Disease Research Center at ASU Biodesign Institute, has been working on this and joined The Show to discuss.

Full conversation

MARK BRODIE: Ben, it seems like you found a new type of Alzheimer’s disease, is that right?

BEN READHEAD: Yeah, we think so. So yeah, we think we’ve identified a novel subtype of Alzheimer’s disease that affects somewhere between maybe 25% and 45% of patients with Alzheimer’s disease, and it seems to be associated with a chronic gut infection with a common herpes virus. And that herpes virus seems to, in a subset of people for reasons we don’t really understand yet, sets up a chronic infection and then, appears to then pass into the brain.

BRODIE: But it seems as though that takes a little while, right? Like this is a virus, if I’m understanding correctly, that people tend to get, you know, fairly young in life. But of course, for many people, if they develop Alzheimer’s, it happens many, many years down the road from that.

READHEAD: Yeah, exactly right. So by the time someone is affected by Alzheimer’s disease, let’s say in their 70s or 80s, maybe 70% or 80% of those people will have some antibody evidence of this particular virus. And so, you know, it’s, it’s a ubiquitous virus, we all come into contact with it. So there’s additional factors that we need to understand to know why it is behaving this way in a subset of people.

BRODIE: What’s the relationship between this virus and dementia later on?

READHEAD: So we’re still determining that, you know, because it really isn’t a subset of people where we see this virus, setting up a chronic infection in the gut. And, and it’s that which seems to be the relevant feature for whether or not it then passes up into the brain. So, most people that are exposed to the virus and have some evidence of exposure won’t end up with it in the brain, according to what we’ve seen in our studies.

BRODIE: What are the implications of this for potentially treating Alzheimer’s, at least for this subset of people who might have it because of this infection?

READHEAD: So yeah, we’re really excited to work out what this means clinically. So, one of the things we, we would like to organize is a clinical trial in patients that happen to fall into this group of Alzheimer’s disease and see whether or not there are some existing medications like antivirals, which we know and are safe and they get into the brain, to see whether or not, it can have a beneficial effect for them.

BRODIE: Are there symptoms that come along with this? Like, is there a way, you mentioned that a lot of people are exposed to this virus. Is there a way to know if it is causing that chronic infection that could potentially lead to Alzheimer’s later on?

READHEAD: So this is something we’re really trying to get to the bottom of right now. So, when we first kind of got down this track scientifically, we were trying to work out what’s different about these patients compared to other patients with Alzheimer’s disease. And we looked along the common dimensions of, you know, age, sex, you know, different disease dimensions.

And really, the key difference that we saw was the difference in antibodies, particularly antibodies that are targeted against this virus that we’re looking at. And so we think it’s gonna ultimately be a blood test, we think, that’s gonna allow us to identify who is in this group and who isn’t in this group. In terms of like clinical or symptomatic differences, we’d love to find something like that. We’re looking for it, but we haven’t found it yet.

BRODIE: And it’s probably important to stipulate that as you say, a lot of people are exposed to this virus, not all of them will eventually develop Alzheimer’s. Do you have a sense of how many people this might be who, you mentioned it could be 20% to 45% of Alzheimer’s patients are in this group. Do you have a sense of how many people who have this infection ultimately develop Alzheimer’s?

READHEAD: Yeah, that’s a great question. It’d be a real minority of individuals that are exposed to this virus because the exposure by itself that doesn’t explain what we’re seeing. There’s some additional failure in the immune system, we think that’s happening peripherally, probably at the level of the gut that we need to understand. So it’s exposure plus whatever else is going on that allows this chronic infection to set up in the gut. That’s the thing we really need to understand, which we’re working, working towards at the moment.

BRODIE: Does this finding suggest to you that there might be other subsets of Alzheimer’s, maybe other viruses or other external factors that might lead people to develop this later in life?

READHEAD: Yeah, I really like the way you’re thinking there and, you know, it’s more speculative at this stage, but you know, if, if I’m allowed that speculation, I think a story like this and others that are emerging in the literature, I think, point to certain sorts of vulnerabilities we should be systematically looking for in diseases like Alzheimer’s and also other, other brain diseases where maybe it’s not this virus, maybe it’s not the vagus nerve, maybe it’s not the gut, but you could think about other vulnerabilities that different people for different reasons are going to be susceptible to and that maybe over decades, you know, might end up affecting different regions of the brain in different ways. And maybe that explains some element of the clinical picture that we see with different diseases.

BRODIE: Because that kind of seems to be like the holy grail for people who do what you do, right, to figure out why and how do people develop Alzheimer’s and then try to stop that from happening, right?

READHEAD: Absolutely. Yeah, and Alzheimer’s is a, it’s, it’s a difficult disease in a lot of ways. I mean, it’s complex, it’s, it’s in the brain, which you, which we still don’t understand. But not only that, we’re, by the time someone comes into the clinic, you know, perhaps complaining of memory problems, there’s a one-, two-, perhaps even a three-decade preceding period where there’s probably been changes going on. And so by the time you get to the stage where you’re studying a brain affected by Alzheimer’s disease, disentangling what is cause, what’s effect, what’s compensation for the disease, you know, that’s, that’s a really tricky prospect.

BRODIE: You mentioned the possibility of anti-viral medication. I’m wondering if you think, and obviously this is potentially speculative at this point, but, do you think that the, the medications in that class on the market now could potentially be effective, or might there need to be new drug development to try to specifically treat this infection as it relates to maybe how it impacts the brain later on?

READHEAD: That’s a great question. You know, probably the most, you know, the low hanging fruit is to look at existing medications, you know, so-called drug repurposing, where there are actually some really good antivirals that have activity against this particular virus which we know, are, you know, safe and, you know, have a lot of safety data on and we know that it gets into the brain. And so I think that would probably be the first easiest trial to look at.

But I think in parallel to that, we should also be looking at developing additional therapeutics and depending on what ultimately is revealed as the reason why some people get this chronic infection, you might then also want to think about things that aren’t explicitly antivirals, but things which will bolster the immune system and prevent this from happening in the first place.

BRODIE: What kinds of things might those be?

READHEAD: Well, you know, I think, you know, the ultimate direction there really will come down to what it is that that factor which we don’t understand yet. So let’s say it’s a co-infection with, you know, some other, some other bacteria. You know, maybe you want a treatment for that bacteria, you maybe you need to be making sure that your gut microbiome is kept, you know, within certain parameters.

And, and so depending on, you know, what that landscape looks like, I think it’s gonna determine what sort of intervention, you know, you might want to craft for that. I think if we keep at it and we don’t give up and we don’t lose focus, I think we could be looking at a future where something like Alzheimer’s disease, you know, we feel about it the same way that we do about high blood pressure or or or a common cold, something that we know about that we occasionally have to pay attention to but which isn’t going to dominate our lives.