Making Sense of Microplastics: New Research Looks at How Microplastics Build Up in the Brain and Body

Transcript

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 caregiver strategies. Thanks for joining us.

Dr. Nathaniel Chin: Welcome back to Dementia Matters. Plastic is one of the most widely used and versatile materials in the world. From packaging and utensils to construction and vehicles, avoiding plastic is nearly impossible in the United States. This wide use has some serious drawbacks, one of the largest being the bioaccumulation of microplastics. Bioaccumulation refers to the buildup of contaminants in an organism over time. In this case with microplastics, tiny plastic particles formed by the breakdown of larger plastic items that can be as small as 200 nanometers across, roughly 400 times less than the width of a human hair. These particles have been found in human blood, placentas and even the brain. In a study published earlier this year, looking at how microplastics accumulate in the body, researchers discovered that brains of people with dementia had up to 10 times more microplastics in them than brains that didn't, as well as many other notable findings. Joining me today is the leader of this field of research, Dr. Matthew Campen. He has authored over 100 peer-reviewed publications, largely in the area of cardiovascular health effects of inhaled pollutants. Dr. Campen directs the New Mexico Center for Metals in Biology and Medicine as well as the KL2 Mentored Career Development Program within the University of New Mexico Clinical and Translational Sciences Center. He's also the deputy director and training core director of the NIEHS P42 UNM Metal Exposure and Toxicity Assessment on Tribal Lands in Southwest Superfund Research Program Center. Dr. Campen, welcome to Dementia Matters.

Dr. Matthew Campen: Thanks for having me, Nate. This will be great.

Chin: Well, I got a lot of their acronyms correct, I hope. To begin, I always like to start with a little bit more about you. What first led you to study environmental health and specifically investigate the presence of microplastics in the human brain?

Campen: Well, I mean environmental health has been an interest since I was an undergraduate. I was lucky, I guess. Maybe not luck. Maybe it's that my mom forced me to go get a summer job and she had contacts with the Environmental Protection Agency, specifically the scientific arm of the EPA, which is in the Research Triangle Park. I got to do a summer internship there and I got to study how air pollutants affect the body. That led to me wanting to go into graduate school for environmental health. It was just a fantastic opportunity. That was my origin, was getting to work with the great scientists there at the EPA, toxicologists, environmental health scientists, chemists, et cetera. Then from there, I've had a career studying air pollution, not just what it does in the lungs but how it affects things beyond the lungs, like the brain, like the growing placenta and the fetus. I think I've had a rich career and I've gotten to do a lot of things. Over the past 20 years, this story of microplastics has emerged. I was very skeptical. Because I've studied little tiny particles that are in the air, like diesel, coal combustion, wood smoke–these are really, really toxic. Often in our studies, we use plastic particles as a sort of negative control because they're inert. They're not that toxic. They don't cause cells to die immediately. You have to have really, really high doses to make that effect. I was skeptical, but then you start seeing the trends of plastics accumulating and you realize high doses might not be an aberration. That might be the norm. I've gotten drawn into this field as a result and it just seems like a global imperative in my mind now.

Chin: I appreciate your honesty and talking about your initial skepticism to it. That's an important part of science, right? We have to be able to change with what we find. At what point in this career of yours did you start feeling like, well, actually, maybe there is something here? Is this more recent for you or this happened a decade ago?

Campen: Yeah, it's been gradual and it's sort of like, we'll scratch the surface and be alarmed by what we find. I typically highlight, in 2019, my son, who was in seventh grade at the time, needed a middle school science fair project. I dragged him up pretty close to the headwaters of the Rio Grande and we collected some water there and then in Taos, New Mexico, and then down here in Albuquerque. We did some basic seventh grade level science to look at the plastics. We showed that they increase as there's more human impact but also that even up in the relatively pristine headwaters of the Rio Grande near Creed, Colorado, we were able to find microplastics. It was like, wow these really are kind of everywhere.

Chin: Wow. Can you walk us through how microplastics are able to enter, I guess, first the body and then get to the brain? I mean, you're talking about water too and air. How does it go from the environment to affect us?

Campen: I think most of it's in the food we're eating. I know there's concerns about air, there's concerns about water, but I think most of it's in the food. It led us to question, are we talking about the gut and the brain vasculature as barriers or should we be talking about them as gateways? Because we do see quite a lot in the body. It started occurring to us that they might just be hijacking their way in through the systems we use to absorb nutrients. That's our leading edge kind of concept right now. We haven't fully established this. Other researchers are working on it. The idea is that they come in with our food, with the lipids that we eat, and our body has specific mechanisms that we absorb fats with. We have pancreatic enzymes that digest and emulsify, break these fats down. Then our epithelial cells, the ones in the gut that absorb food, they repackage those as a little particle that goes into the blood and that particle is called chylomicrons. That's our hypothesis and we have a little bit of data on it. But the chylomicrons are important because that doesn't just lead to random distribution from the gut. They actually get targeted to regions of the body that want fats for energy or for structure. The brain has lipids in myelin and throughout. We think that this is part of a very mechanistic, very controlled pathway. It's not about inflammation in the gut. It's not about dementia and inflammation in the brain. It's just normal and that's kind of the concern.

Chin: It seems like this is an essential pathway. It's not like we can alter this pathway in order to reduce this.

Campen: That's a big insight, Nate. That's been one of the concerns when we talk about plastics getting to the placenta and across to the fetus. I don't think we want to interrupt that because it's going to interrupt how we get lipids and energy to the fetus.

Chin: Now, your study found a striking difference in microplastic levels between people with and without dementia. Can you talk more about that? Why do you think that is?

Campen: Sure. We see high levels of these plastic particles in the brain of normal individuals. It was about five to eight times that concentration in the dementia samples. We only looked at 12 different samples from donors. There were, I think, six Alzheimer's disease, three vascular dementia, and then three that we would classify as other dementia. We didn't really see trends within those groups. The vascular dementia trended on the higher side. When we anatomically looked at the samples, there was definitely a clustering that we didn't see in normal patients in and around the arteriolar wall. The vascular wall seemed to have a high amount of these. It brought to mind, look, there's a blood brain barrier deficit in dementia. That's part of it. It could just be a more hospitable environment for the uptake. We also saw it in and around inflamed regions in the brain where there's immune cells. Again, sort of a horse-cart phenomenon. Are we talking about plastics driving a disease or is the disease just a place where the plastics are gonna end up? That's where we are scientifically right now. We don't know if this is a causal issue.

Chin: Well, that's actually going to be my next question. If the evidence isn't there, just based on what you know, do you think it's possible that microplastics found in the brain can contribute to cognitive decline or is it more just a marker that there's already damage and inflammation and issues here?

Campen: I tend to think more of the latter. There's some compelling data from Andrew West at Duke, as well as a recent publication out of China, that the nanoplastics can drive some protein aggregation. Tau, beta amyloid, synuclein may be caught up just as a surface chemistry interaction with the plastics. I don't know that that's really playing out in these cases we're looking at. For now, I'm being very cautious in the interpretation. I think that it's more that the plastics end up there because the barriers have broken down.

Chin: Then can you explain for our listeners how you actually are able to identify, materialize, or actually quantify the plastics in an autopsy brain?

Campen: Oh yeah. We took a variety of approaches because there's no one perfect method. The big quantitative approach is an analytical chemistry instrument called the pyrolysis gas chromatic graph and mass spectrometer. It's a complicated name. It's a mouthful. We call it Py-GCMS for short. Essentially what we're doing is we're isolating the plastics from the brain, we're combusting them at a high temperature, 600 degrees centigrade. Then the gases that come off of that are going to have signature properties that we can then analyze. For instance, polystyrene creates styrene and we can measure that. The nylons release a compound called caprolactam. We can measure that. We're looking for these tracers that are a little bit indirect, and that's a concern for what we're doing. The miracle, I guess, is in the digestion process. We take part of a brain, chemically digest it, and then isolate the plastics as solid materials that are left over. We also do visual analyses. We're using visual microscopy and electron microscopy. We're using Fourier transform and Raman spectroscopy to show chemical signatures of polymers. We're using polarization wave imaging to look for refractile properties of these things. We've had to capture a broad array of approaches to claim with any confidence that we see plastics in the brain.

Chin: Yeah, it all seems very technical. For our listeners, when we say, oh, 10 times more microplastics than before, or five to six times more in someone with dementia than without, can you help us visualize how much is really there? How would we understand what you're quantifying?

Campen: There's a lot of uncertainty in our numbers. I just want to be very clear about that. The horses left the stable around the phrase, the plastic spoon. When we do the math and we say there's about 5,000 micrograms per gram, and we say each brain is about 1,400 grams, you do the math, multiplying those together, and you end up with seven grams. That's a lot. There's reasons why that's probably high. There's reasons why it's probably low. It's complicated. One of the reasons it's high is that lipids in the brain might be causing sort of a false positive. That's part of it for polyethylene, probably not part of it for polypropylene. That doesn't interfere on the mass spec. Another reason it might be high is that we've now started mapping how much plastic is in all the parts of the brain, and we started with the frontal cortex. In mapping the rest of the brain, it seems that the frontal cortex is quite high for probably a couple reasons–metabolic needs, myelin, things like that. Our analogy to the plastic spoon might be analogous to if you did a population estimation of the United States by a random sample that you took in Manhattan. Maybe Iowa doesn't have quite that many people in it. Maybe Nebraska has a lower population. Looking at the rest of the brain, we definitely see quite a lot lower, especially mid-brain, hypothalamus seem to be lower. We're still figuring things out.

Chin: What other significant findings, though, did you discover? Because it wasn't just what we've been talking about.

Campen: Probably the biggest outcome of that paper is the change over time. We looked at samples. These are all cadaver samples. We looked at individuals who died in 2016 and individuals who died in 2024. There was a significant increase of about 40 to 50 percent over that time period, eight years. The reviewers of the paper held our feet to the fire and said, you really need to spread out that timeframe. We worked with an investigator at Duke, Andy West, and we were able to get earlier time points and they were lower. Now, admittedly, there's a geographical difference because our first cohorts were in New Mexico and the others we added were from Maryland, North Carolina, that area. The trend line didn't change when we added those other samples in there. It's not a crazy concept that plastics are going up in our brains over time. In fact, it's obvious. If you've got brains from 100 years ago, they didn't have plastics 100 years ago. Today we do. I think it's a little alarming to see that over just an eight-year window, we are seeing a change that's substantial. I mean, 50 percent is a lot. If that continues, we have reason to worry.

Chin: That does seem like a pretty extreme amount. Do you think that this is because we're just exposed more and more to microplastics in our food that this is a direct consequence of whatever the food production system is?

Campen: I think so. You've got a situation where we've been making plastics more and more every year. The doubling time for plastics production has been about every 10 to 15 years. It's exponential growth. The transformation from plastics we use to micro and nanoplastics probably takes years, if not decades, for some different types of plastic. I've got plastic items in my house that are probably decades old right now–coffee makers and buckets and planter boxes and things like that are still hanging on. Eventually they'll get thrown away. In the environment, in landfills, they get broken down, they get into our water system. We put that on the agricultural fields and it enters into our dietary pathway. That process might take decades. What we know from the production and the exponential curve of production, we anticipate there will be some mirroring or parallel, but decades later. That's a big concern. If we're worried about this now, even if we could quit plastics, which I highly doubt–I want to point out that I know you're not going to use the visual and for me to use air quotes around "quit plastics" is problematic, I should mention it– but if we were to get rid of plastics immediately right now, we would still have to worry about microplastics for decades, generations of humans to come. We need to be very thoughtful about not just reducing production, but what do we do with the waste management? What's the path of this getting into our system? That research needs to be done. I'm glad there's been recent legislature introduced–bipartisan legislature in both the House and Senate–saying the USDA, NIH, HHS, they really need to start putting resources to understanding this before we don't have an opportunity to change course.

Chin: Yeah, this really has a lot of social, environmental, cultural policy implications, Matt. This affects all of us. You can't hide from plastics.

Campen: We can't, and we shouldn't. There's demonstrable benefits of plastics. I don't know how to administer IV fluids without a plastic bag, colostomy bags, the opportunity to provide sterile anything in the clinic. We need plastics for it. It does require cooler heads prevailing. I appreciate that there's a lot of really solid advocacy raising awareness on this issue. It needs to be addressed by the government. It has to be a federal issue. It can't be a system where we're guilting people into recycling into a system where we don't know if it works or not. We can't expect people to go into the grocery store and reduce their consumption when there's no choice but to buy things in plastic bags. I think it needs to be addressed at that higher level now.

Chin: In your findings, what types of plastics were most commonly found in brain tissue or does the type even matter?

Campen: Both good questions. We have a way of looking at 12 different major types: polyethylene, polypropylene, polyvinyl chloride. Those tended to be the highest, polyethylene by far. That might be influenced a little bit by the residual lipids, so maybe we're overestimating polyethylene. We tend to see a lot of things. Styrene-butadiene rubber, which is probably coming from tire wear in the environment. There's a lot of that. We see nylons. A little bit of polycarbonate, polystyrene–those are much lower, probably not even significant factors. To your point, I don't know that that makes a difference once it's inside the body. Plastics may behave the same in terms of how the body responds to them. It's also very likely that they don't look like plastics anymore when they're at this stage of degradation. If you have an old piece of plastic–and I think about, I've got this Adirondack chair that's been sitting in my backyard for probably a decade, and it just has this scratchy film of white degraded goo around it–I think most of the nanoplastics especially are going to be like that. They're going to have this layer of aged organic chemical that used to be polymer, but so much oxygen has bombarded it. It's broken. It's not a polymer, might be a chain of 6,000 carbons. These are probably much shorter chains with lots of oxygen. If it comes through the food system, there's going to be other elements like magnesium and calcium and things like that that are on it. It's going to look very, very different, and how the body handles that, you might not be able to tell the difference between a polystyrene and a polyethylene anymore.

Chin: I know there was a limited sample, but was there a difference in microplastic accumulation based on the age, the gender? You mentioned region, so region seems to be important.

Campen: So far, we don't have a lot of insights into this. Age didn't seem to be a factor really. That was surprising. We had ages from essentially youth until very, very old age. We would have expected that there's some accumulation over time or over age, and there wasn't. There was a difference if you died in 2016 or you died in 2024. If you died in 2024 and you were 18 years old versus 84 years old, didn't matter. We think that there's some equilibrium that hits and it's possible that your body is clearing this through normal pathways, whether that's through your kidneys, you've got a hepatobiliary recirculation that might be putting these back in the gut for you. It's also possible that these nanoplastics are degrading in the body. Some of our images that we've been collecting recently make it look like these things tend to shred a little bit. They're these flat little flakes or shards and they're still durable. We bombard them with lasers with the transmission electron microscope and they're still durable but we do see evidence that they are starting to fray apart. Over time, they could degrade in our body.

Chin: Do you tend to see more microplastics in the kidneys and liver, perhaps because it could be cleared or broken down that way?

Campen: I won't say more, but what I'll say is that when we look anatomically at where they're located, it's in the path as if they're being handled, for lack of a better way of phrasing that. Kidneys filter your blood through the glomeruli, and that's where we see a lot of these things. We also tend to see a pattern where they're flowing down the distal tubule. So, good news, right? There's been relatively limited success in measuring plastics in the urine because we think it is relatively low concentration. We're starting to do that now to get a better handle on it. It's hard. I think we've found that it's easier to find plastics in solid organs like the brain, liver and kidney than in the fluids like blood and urine just because the concentrations are much lower at any given time.

Chin: What are the biggest unanswered questions that came out of your research?

Campen: So many. I think that the nanoplastics issue is a very contentious point on this. What are nanoplastics? People have really not visualized them very well, and we're not sure. There's a really cool paper that just came out this month from Sophie ten Hietbrink out of Europe, and it's in Nature. It's a cool paper where they're looking at the concentrations of nanoplastics in the North Atlantic. The upshot of that paper, not that we're drinking water from the ocean or anything like that, but the upshot of the paper is that there's more nanoplastics potentially, by weight. That's key. By weight, there's more plastics in the nano fraction. We can't visualize nanoscale. You need an electron microscope. We can't do the chemical signatures from spectroscopy with that, like FTIR and Raman. 20 years of literature around microplastics doesn't really teach us anything about nanoplastics. The idea that they're seeing more nanoplastic in the ocean than microplastic is alarming because that means it's sort of this dark matter. Our data from the body is very similar in this manner. When we isolate and image the solid material from the brain or from the kidney or liver, it's nanoscale. It's only nanoscale. It's the size of viruses, 200 nanometers by 50 nanometer shards. I think that's the biggest thing that has been uncovered and needs more detail, because if we're going to quantify this, if we're going to start relating this to human diseases, we need to do a much better job with the nano.

Chin: Earlier, I was going to ask you what your lifestyle is like just given your work with plastics. You've already answered that. You use plastics, you have them. You sit in an Adirondack chair. For people who are listening, is there a way–or would you even recommend–that they try to find ways to reduce their exposure to microplastics in the day to day?

Campen: Everybody should do what they can. People should not go to extremes that are unhealthy. That’s the way I put it. I know people worry about this a lot and it causes undue stress and cortisol, and there's known health effects of that. I'm happy with my lifestyle. I walk to work. I have solar panels. I'm doing what I can to achieve a sustainable footprint but it's impossible. You're a human, you're part of this planet. You just have to accept to some extent that there might not be anything you can do. With regards to the microplastic story, we really need to think more practically. Recycling it into a system that may be shipping it overseas, that's a ridiculous way to approach this. I don't know if you read–there was a great editorial in The New York Times a couple months ago that said, "The Story You've Been Told About Recycling is a Lie." I love the perspective that this plastic started under the sands of Saudi Arabia, got pulled out and shipped across the planet to what we call Cancer Alley in Louisiana, gets refined into ethylene, transformed into polyethylene, and then turned into a plastic bottle, which gets filled with water. It sits on a shelf for years potentially. I always have this plastic prop. I'm showing you, Nate, this plastic bottle. I could probably drink this in about 45 seconds and then it's done. It means nothing to me. This plastic bottle meant 45 seconds in my life and that's it. Then it goes on another journey across the Pacific to Bangladesh and eventually gets set on fire. What a ridiculous amount of energy that one little article consumed and it meant nothing to the user. It's crazy. It's crazy and we've let this happen. There's now this huge economy around it. I've just gone off on a huge tangent to a simple question about what do I do in my lifestyle. (laughs) I haven't changed a lot. I try to live simply. I have a love for my little pottery mugs and solid objects that I put fluids in, but not much.

Chin: Well, I mean, I appreciate what you said about living sustainably, having as small of a footprint as is reasonable and doable. I think that is something for all of us to strive for. I do really like your story of the water bottle. I hadn't thought of it that way, but you're right. 45 seconds of something we don't really think about and all the energy that went into it. Well, to end, where does your research go from here? Are you looking at other longitudinal studies? Are you looking at interventions? I mean, what is your next step after finding these important results?

Campen: The immediate question around nanoplastics is something our team is focused on. I think we'll have some answers for that soon and get that published. There's tremendous interest. One of the benefits of the attention we've gotten over this work has been a lot of great research teams around the country and internationally have reached out to us to do collaborative work. I have infinite interest in biomedical research and the opportunities that we can help people understand. Are there plastics in glioblastoma? Are there microplastics involved in the processes of dementia, Parkinson's? Do people with TBI, CTE absorb more plastics? Then there's also glioblastoma cancer, breast cancer, colorectal cancer and appendiceal cancer. All of those are trending upwards. You talk to the oncologists and they're like, these cancers are occurring in younger people and they're more aggressive. This is just what I'm seeing in past 10, 15 years of practice. We're talking with people about autism spectrum disorder. We're talking with people about reproductive health, placentas and transfer through to the fetus, cardiovascular diseases, autoimmune diseases. I am just really excited to be involved in so many different things. It's just opened up so many books here.

Chin: Well, we look forward to your future work and publications, and then we'll have you back on when you come out with your next findings, Matt.

Campen: Okay, that sounds great, Nate.

Chin: Well, thanks for being on the show today. We'll be seeing you in the future.

Campen: All right, that sounds great.

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