Where’s the Connection? The Role of Synapses in Memory and Alzheimer’s Disease

Synapses are points in the brain where two brain cells connect and communicate. Dr. Barbara Bendlin discusses her new research into synaptic change, its relationship to memory loss, and how her first-in-the-field research might one day lead to a new tool for early diagnosis of Alzheimer's disease. Guest: Barbara Bendlin, PhD, Wisconsin Alzheimer's Disease Research Center

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Barbara Bendlin, PhD

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Intro: I'm Dr. Nathaniel Chin, and you're listening to Dementia Matters, a podcast about Alzheimer's disease. Dementia Matters is a production of the Wisconsin Alzheimer's Disease Research Center. Our goal is to educate listeners on the latest news in Alzheimer's disease research and care givers strategies. Thanks for joining us.

Nathaniel Chin: Today's guest on Dementia Matters is Dr. Barbara Bendlin, an investigator with the Wisconsin Alzheimer's Disease Research Center. Dr Bendlin studies how various aspects of health contribute to increasing or decreasing risk for Alzheimer's disease. Her research has examined gut microbiome, exercise, diet, diabetes, and many other aspects of health and how they intersect with Alzheimer's disease. Dr. Bendlin, welcome to Dementia Matters.

Barbara Bendlin: Thanks. Happy to be here, Nate.

Nathaniel Chin: So to begin, you have a new five-year grant from the National Institute on Aging to study Alzheimer's disease from a very unique perspective -- by using advanced brain imaging to track how synapses in the brain change over the course of Alzheimer's disease. Can you start by explaining what are synapses, and what will they tell us about the course of Alzheimer's disease?

Barbara Bendlin: So if you've ever heard of the concept of two brain cells connecting to one another, then you're familiar with the concept of a synapse. So synapses are the point where two brain cells meet with one another, and that's the point where brain cells can communicate with one another and send messages with one another. The reason why we're really interested in synapses is because we know in Alzheimer's disease and other neurological illnesses, people lose synapses -- they lose these connections between brain cells. And it's actually the case that when we look at memory function and other thinking skills, that synapses reflect loss of function. So when someone loses memory that's reflected by loss of synapses.

Nathaniel Chin: And so a synapse isn't just a place in space, it's an actual material from our brain cell.

Barbara Bendlin: Yeah. Brain cells, also called neurons, connect to one another. And actually synapses are a tiny, tiny little space between the two brain cells where they send messages, kind of across a little space.

Nathaniel Chin: So brain cells are not actually touching each other.

Barbara Bendlin: The brain cells are not touching one another at the synapse.

Nathaniel Chin: So on average there are about 100 billion neurons in the adult brain. So what does that mean for synapses? How many synapses does an adult have?

Barbara Bendlin: So 100 billion is about an estimate. There was actually a recent study that suggested it's more like 86 billion neurons, which is still a lot. And the amount of synaptic connections is trillions. So we think there's probably about 100 trillion synapses in the brain, so brain connections.

Nathaniel Chin: Wow, so there's already a lot of brain cells, neurons, but now you're telling me there's a significant amount of these connections.

Barbara Bendlin: Correct. And the interesting thing about synapses and why they're important is because if you think about memory function, essentially everything that you learn or your experience or your sense of yourself is all coded in the brain and these connections between the brain cells. So everything that we remember from either today or you know, anything you learn on this show, that's going to be coded in your brain in the form of these synopses.

Nathaniel Chin: Wow. I mean this is a real change in how a person thinks of a brain as just tissue and there's a cell here. But now we're saying that real important information can be stored in the synapses, which is really the connection between our brain cells.

Barbara Bendlin: Exactly. So brain cells fire. They fire together. They send electrical and chemical messages. And when we think about a memory or we have a memory, it's essentially stored in the brain in the form of these patterns of brain firing and the connections between the cells. So some people want to know, can you grow synapses, for example. We do form new brain connections when we learn material, and when we learn things and that material is repeated, then those connections can be strengthened.

Nathaniel Chin: I think that's a really important idea though. So not only can we grow new brain cells, we can grow new synapses, but the more we do something, the stronger the synapse is going to be.

Barbara Bendlin: Correct. So if you think about a hiking path, a trail in the forest, if that trail is used very often, then it becomes more prominent. You can see it better. It's a stronger trail in the forest. If we stopped taking that path, and it becomes overgrown, it becomes more faint, eventually it disappears. So it's kind of a similar concept with memories and things that we learn. If there's a lot of repetition, it becomes a stronger pathway.

Nathaniel Chin: So is it fair to liken it to athletes who have really impressive muscle memory? They can shoot a three pointer without really looking because they've done it so many times before.

Barbara Bendlin: Absolutely. And that's, that's a form of motor memory.

Nathaniel Chin: Okay. And then the same idea of, you know, I talk to my patients a lot about cognitive enrichment and learning new skills, picking up a new hobby, with this idea that you're challenging your brain, you're building stronger connections in different synapses.

Barbara Bendlin: That's exactly right. You had also mentioned that we grow new brain cells. It's important to clarify that we don't grow a lot of new brain cells. There's a little bit of new brain cells produced. It's something called neurogenesis. But that's a very small number of cells. Really in terms of of brain change, we should think more about strengthening these connections, or forming new connections.

Nathaniel Chin: Which really shows the importance of looking at synapses, since this is something that we can do and we have some control over by how we're activating our brains.

Barbara Bendlin: Absolutely.

Nathaniel Chin: We so knowing that, what exactly are you studying in your project?

Barbara Bendlin: We have a brand new brain imaging technique. The technology that we use is PET [positron emission tomography] imaging. And what it can show us is synapses in a living human brain. And this is super remarkable. It's not something that we were able to do previously. It's a newly developed technique, and we have the capability here in Wisconsin to do this kind of imaging. It's really a first for the field, and we're very lucky that we can do this in Wisconsin.

Nathaniel Chin: Knowing that there are 120 trillion synapses, and that it would be very difficult on a image to see individual ones, what exactly will you be looking for and where will you look for it?

Barbara Bendlin: What we're looking at is synaptic density. So if you have more synapses in a brain region, on our test it will show up as a brighter area. And what's been shown now in a few cases of people who have dementia due to Alzheimer's disease, it's been shown that certain areas of the brain lose synopsis and that can be seen on these kinds of images. So what we want to do here is scan people who both have dementia due to Alzheimer's disease, but also people who are without Alzheimer's disease and kind of see what do these images look like as people get older and as they start to develop disease.

Nathaniel Chin: So how large is the study?

Barbara Bendlin: We are going to enroll approximately 120 people. The study is funded for five years. We're asking people to come in twice, separated about two years so we can see if there's any change over time. And we are asking people to come in who have normal memory, people who have mild cognitive impairment, so some memory impairment, as well as people who have already been diagnosed with dementia due to Alzheimer's disease.

Nathaniel Chin: Will this study only occur in Madison, or are there other places that this will also take place?

Barbara Bendlin: So this is a very new technique. There's not a lot of centers that are yet using this imaging technique. In Alzheimer's disease, the two centers that are using it are Yale University as well as Wisconsin. So we'll also be working very closely with their group to compare notes.

Nathaniel Chin: So what kind of information, if any, will you share with the research participants in this study?

Barbara Bendlin: That's a really good question. So at this point, we don't know if this scan can be used clinically. You know, does it tell us information that's clinically important? So at this point in the study, we won't be sharing back the results of this particular scan. That said, this research is really, really important for determining if it can be used clinically. And there's a lot of people in the field who feel that this particular scan has a lot of promise and that it could eventually inform clinical decisions, and that it could potentially be used to help identify people who might be eligible for certain clinical trials or even to use it as an outcome measure to see if a new drug is working for Alzheimer's disease.

Nathaniel Chin: Well, so how will this particular type of scan compliment the other ones that we currently do in research and some of which we do in clinic?

Barbara Bendlin: So we currently actually have a lot of tools to understand how Alzheimer's disease is developing in the brain, mostly from a research stand point. We use techniques to look at brain volume, you know, how much is the brain shrinking over time, for example, or are there other pathologies present? Is amyloid pathology developing, which is a key feature of Alzheimer's disease. The really interesting thing about this synaptic tracer is that it should be able to show us changes before we see changes on MRI [magnetic resonance imaging] for example. So on MRI you would need to lose a lot of brain cells before we can see that a region is shrinking. This tracer is very sensitive so it should be able to tell us if people are showing very early either loss of synapses or loss of brain cells perhaps before an MRI would be able to show us that information.

Nathaniel Chin: And when we talk about intervention and wanting to get people earlier and earlier in their course of disease, hoping that that will make a big difference in the long run, this could be a study and a scan that we could use.

Barbara Bendlin: Well that's what we think. And again, you know, it's a research study and we at the very, very beginning. But if it really is sensitive to synaptic loss, which it should be, then we may have a very game changing technique on our hands.

Nathaniel Chin: Well, because right now, are there any other ways of detecting synaptic loss, whether it's through the blood or the CSF, the spinal fluid?

Barbara Bendlin: Yeah. So there are some techniques that have been developed. Honestly the main way that you see synapse loss is when you look at the brain after death. That's been the main research technique. There's now new assays that have been developed for cerebral spinal fluid and those also look very promising, but they're not yet clinically available, or fully understood. And there's no blood based biomarkers. That would be ideal if we could do a blood test, but those aren't available yet.

Nathaniel Chin: It starts with showing it through imaging right now.

Barbara Bendlin: Correct. Yes.

Nathaniel Chin: Are scientists studying synaptic change in relation to other brain diseases, such as Parkinson's disease?

Barbara Bendlin: There is definitely interest in using this technique for other neurological diseases. There's some emerging work in Parkinson's disease. There are some small studies testing it in Parkinson's. It has also been tested in epilepsy. And also, interestingly, in disorders of dependence or drug dependence because we know there are certain brain circuits that lead to addiction. So there has been a lot of application in addiction. And most of this work has actually been done so far at Yale University.

Nathaniel Chin: Well, so in closing, how do you expect the results, or how do you hope the results, of your work will contribute to treatments for halting or preventing Alzheimer's disease?

Barbara Bendlin: What's really exciting about this technique is that we're imaging the part of the brain that is responsible for memory. So you know, we have this opportunity for the first time to look at the part of the brain that's important for our sense of self, for our life history, for our memories. And it's really the part of the brain that we want to protect and preserve. So the idea is that we can use this technique to see how those changes are happening in Alzheimer's, but then also test drugs that could protect this part of the brain. And a lot of the studies to date have focused on removing amyloid from the brain or targeting amyloid, which those studies are also very important, but there is some suggestion that synapse loss could be a very, very early feature of the disease. So can we develop techniques to protect this really important part of the brain and save memories?

Nathaniel Chin: Well, this is incredibly important and very exciting, and I'm glad it's happening here. So with that, I'd like to thank you for being on Dementia Matters, and we hope to have you back after you get more results.

Barbara Bendlin: Thanks for having me, Nate.