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Welcome to the Healthy Brain Toolbox. I'm Dr. Ken Sharlin, neurologist, speaker, author, and host for this show. In each episode, I interview influential people whose work impacts how we live and how we think. My guests are leaders in the health and fitness industry, physicians, scientists. Here, you'll find conversations that break down barriers, expand your horizons, and give you the tools you need to protect your health and nourish your aging brain.

Dr. Ken Sharlin: 0:31

Welcome today on the Healthy Brain ToolBox. I am joined by Dr. Rany Aburashed, a neurologist, a medical innovator, an entrepreneur who's helping to redefine how we detect Alzheimer's disease. Dr. Aburashed is the Chief Medical Officer at Insight Hospital and Medical Center in Chicago, where he leads neuroscience programs and specialty care expansion across the system. He's also the CEO and founder of Neurogen Biomarking. This is a company pioneering at home blood-based biomarker testing, combined with digital cognitive assessment tools, giving patients and clinicians faster, more accessible ways to detect early signs of Alzheimer's and mild cognitive impairment. He trained in neurology and neuroimmunology at Michigan State University College of Osteopathic Medicine, and over more than 15 years in clinical practice, he's been deeply involved in research spanning multiple sclerosis, neuro degeneration, and biomarker driven. Neurodiagnostics. What I find so exciting about Dr. Aburashed's work is that it sits right at the intersection of precision medicine, digital health and accessibility, bringing sophisticated neuroscience into people's homes. So today we're gonna trace the evolution of Alzheimer's diagnostics from. Earliest discoveries of plaques and tangles to PET imaging, blood-based biomarkers, and now this new frontier of home-based testing and explore how Neurogen Biomarking is helping make that future a reality. Welcome to the Healthy Brain Toolbox. It is so great to have you here.

Dr. Rany Aburashed: 2:22

Thank you so much for having me.

Dr. Ken Sharlin: 2:23

Before we dive into cutting edge science, I'd love to start with a little bit of history. More than a century ago, Dr. Alois Alzheimer's described those hallmark plaques and tangles in the brain. So from your perspective, what's the through line from those early autopsy findings to the molecular precision tools we're using today?

Dr. Rany Aburashed: 2:46

Yeah, I think it's a beautiful question and I think it's a great place to start because it gives us the ability to really see at a hundred thousand feet what's happened when you look back in, in 1906 when Dr. Alzheimer's, was looking at autopsies under the microscope and really first characterized that these are tangled proteins and plaques that are connected to people who had a devastation in their memory. And then you start to fast forward. It clearly was, the science at that time could describe what had happened, but it couldn't intervene in time to change it. That's where we sat in 1906. If you fast forward to today, for example that exact biology, those same hallmarks that were described, we're seeing those now in a single drop of blood. And so if you pause and think about the gravity of that, what he was witnessing under that microscope in a deceased patient, we can now measure in living people at the most. Finite molecular level. And to me, the through line in all of this is that for a hundred years, we're always looking back. And for the first time now, I think we're looking forward. We're able to detect, we're able to predict, we're able to potentially prevent this disease. And it really shows you that discovery which at the time was remarkable was just the beginning of the story. Not the end of, Hey, here's this disease which is very exciting as a clinician and as a s scientist.

Dr. Ken Sharlin: 3:58

I see the challenges in the accuracy of the diagnosis of Alzheimer's as much. A sort of cultural thing if almost not more than really a scientific one, given the availability of this, where the science is today. Because in my clinic, there still seems to be a lot of confusion in the general public about how difficult. It is to diagnose Alzheimer's accurately and what folks think is really required. I'm sure you have too. I thought that, the only way to be sure that person had Alzheimer's is you have to wait till they die and look at the brain under the microscope. And we do know from some published papers that the clinical diagnosis of Alzheimer's.

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Dr. Ken Sharlin: 6:36

What would you say are some of the biggest challenges clinicians face when trying to make that call early and with a lot of confidence?

Dr. Rany Aburashed: 6:44

Yeah, I think you're hitting the heart of what the issue is in Alzheimer's, which is that with everything we know today and all the work we've done in the neurologic field. Diagnosing it early is incredibly difficult and notoriously inaccurate. In the current clinical infrastructure of how we practice medicine the reality of the disease is that, the symptoms start very subtly, a misplaced name here or there, forgotten appointment. And most of us can explain these things off as normal aging, your stress or my sleep's not great. And then by the time that memory loss becomes clearly, unmistakable. Years and sometimes even a decade have occurred. Underlying all of that, you have this silent biology that, that's occurring in the brain, the one we described previously. So from the clinician side, I think that uncertainty is painful. We really want to help people early, but our tools at least recently up until recently were either too subjective, too late, or we just couldn't really get access to them. And so a lot of docs I think are left, making this sort of. Gestalt, best guess diagnosis. And that's really hurt. I think the way that we've been able to conquer the disease. To me the new era of this biomarker driven testing does give us an opportunity. It changes everything in terms of how we approach it. We're able to see fingerprints at a molecular level years before symptoms are severe. And we're able to react and anticipate what, what may come. And then even, getting people in clinically in, into where they need to go for confirmatory testing is really where we're going. At the core of all this it's not just about diagnosing Alzheimer's, it's really about giving people really back. The one thing that this disease does, which is it steals time. And we're coming into an age now where I think we will improve upon this. But yeah in the current infrastructure, it's really not very well done. I think all neurologists can admit that, even the best neurologists in the country, it's really tough to do without the right tools.

Dr. Ken Sharlin: 8:26

Absolutely. But getting better. There's light, there's the shining light here, there's the hope. It is definitely moved into the modern age. We just have to get a lot more folks on board. if someone came to me with concerns over cognitive impairment. The sort of very basic evaluation, good history, a physical exam, maybe a pencil and paper, cognitive test, the St. Louis University mental status, the mini mental status. We use the Montreal Cognitive Assessment. There are other platforms of course out there, but in the end, we're doing some lab testing. We're tested, B12 folate, thyroid, sedimentation rate. We send folks for an MRI, and that's where I'm heading because. MRI has certainly come a long way. We have better and better magnets, higher resolution but the traditional MRI, meaning this sort of, gestalt let's you know it takes a radiologist. Look at this and describe what they see. Without objective metrics, meaning without quantitative volumes is actually a pretty weak test. And if some of has lost a tremendous amount of brain volume they're probably a lot further down the rabbit hole. Than the stages we're talking about. MRI is really a fairly weak tool unless you start introducing those volumetric additional volumetric software that's not widely available. So then we have PET scan and PET kind of came into the picture in terms of Alzheimer's. Probably in the early approval of amyloid tracer and PET scan. And I tell my patients that, MRI is about anatomy, but PET is about how the brain is working, or in this case, the ability to identify one of the classical biological markers in the brain. The companies that develop these FDA approved tracers. They were in a bad situation'cause they made a huge investment and even though they were FDA approved, CMS had no interest really in creating a reimbursement structure around that. So we were still stuck for many years without the ability to use amyloid PET scan in clinical practice. I just wonder if you can talk about that disconnect between the science and the policy and how that policy affected real world care.

Dr. Rany Aburashed: 10:41

Yeah. I think this is a very important point and I think it it's not unique to just PET scans, but I will talk about amyloid PET specifically because I think it was really bittersweet moment, I think for all of us in the field, right? when Amyloid PET first got approved. It was really the first time that we could actually see a disease unfolding, right? Like in a living brain. And so decades of science sort of were coming to the table and being brought together in this amazing research. and then the reality was patients just couldn't access it. CMS at the time didn't cover the scan. And so outside of research, really nobody could get it. And I think it's an example of a lot of things in the medical field where you have this incredible diagnostic breakthrough. It's something that could finally separate Alzheimer's from other causes of cognitive decline because it's not just that you're diagnosing Alzheimer's accurately. There's other reasons that could be causing cognitive decline, some of which potentially are reversible. And this technology sitting on a shelf outta reach. I think the disconnect between science and policy creates a real human cost for all of us. We are very rigorous in terms of how we validate these things and we'll talk, I'm sure at some point today about biomarkers specifically, And how much works have gone into getting these things to the real, to the table. But at the end of the day, it really affects a lot of things downstream. For example, not having access probably slowed a ton of clinical trials where we would've been able to get the right patients into those trials to see if molecules might actually help Alzheimer's. So I think to me, that's one of the big lessons of the era is that, and that's really why I started building this company, is that innovation. Only matters when it's accessible. If we have the cure to a disease, but we can't get to the disease in time, then we have nothing. So I think that's how we push and it's how science is going.

Dr. Ken Sharlin: 12:15

Yeah, it is. And of course as a neurologist, we had to suffer through many years of the reputation of diagnose and adios. The most advancement, I'm sure you would agree in terms of the neurology space has been in multiple sclerosis. We have remarkable number of disease modifying therapies that really do, particularly with the B-cell depletion therapies, put a major dent in the progression and the relapse rates and people can do extremely well with these drugs. But we're far from it, even with the currently approved. Drugs on with Alzheimer's. But it's interesting, a few years ago when Biogen got accelerated approval of AGI Helm or Aducanumab no longer it's essentially no longer commercially available. I think it is for like compassionate use or somebody who had started on it and they still want to continue with it. But at any rate, that was more of a bus business decision than a, than an efficacy decision to pull the drug. But I remember, visiting with some of the reps as, as Biogen built out their team and they came to my office and they were shocked because I know we haven't quite touched on this yet, but they said at the time there was still no approval. Two or three years ago, there was no reimbursement approval for Emily PET. And so we were depending on, those of us who were interested in biomarkers were depending primarily on spinal fluid. And they said, we are beside ourselves because we're visiting these neurology clinics and then neurologists aren't doing their lumbar punctures, like, how are we supposed to make the diagnosis? It was like, it was insane. So amyloid is a piece of the puzzle. It probably is not really per se, the cause of Alzheimer's disease, but it is a player, the accumulation of the toxic amyloid, the proto fibrils to mature amyloids, certainly may represen. Part of that pathological process. But there is also another piece that we probably need to talk about because ultimately all of this plays into blood-based biomarkers, and that is TAU and there we do have tau tracer also for PET scan, another powerful tool.

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Dr. Ken Sharlin: 16:24

But here, reimbursement is still essentially non-existent. I'm curious why you think tau, especially as it's emerged in the form of the ptal 2 17 and the 180 1. Why it is that we're struggling so much to get coverage for this?

Dr. Rany Aburashed: 16:40

Yeah. This is a great question and I'm glad you brought it up, because to me this is at the core of the cutting edge of where we are with Alzheimer's tau imaging. It allows us to see not just if amyloid is there, but really we can see how far the disease has progressed inside the brain. It correlates much better with symptoms and I think it's a better molecular reflection of how much damage has actually occurred in the brain. The challenge, I think, comes down to the same thing we discussed earlier, which is practicality and policy At this point yes, it's scientifically powerful, but is it accessible? it's expensive. it requires, special equipment to get it done right. And it's just at this stage not scalable for the average patient. Obviously reimbursement remains limited. And so I think it's just another example of how science sometimes just races ahead of the system that supports it. And obviously clinicians, I think if they're educated on this, would want to use these tools. But until they're accessible, it's gonna really be a challenge for people. That really is, the crux of why I think where we're headed now. the blood-based biomarkers and, I think that's everything. And I'll elaborate on that, I'm sure as we continue the conversation because it is a huge window of opportunity for us that I'm very excited to at least, play a role in some degree.

Dr. Ken Sharlin: 17:49

Yeah, and I know we don't wanna necessarily dwell on the PET tracers, but I, I just, I think you're making an important point. And as somebody who sits in the chair of hospital administration, ancillary services and things like that, probably getting a PET and or rather an amyloid and tau PET scan, you're probably talking, a lot of folks don't know that these tracers have to be produced by a cyclotron. They have to have a certain amount of radioactivity to ultimately be used clinically.'cause if they lose too much of their radioactive level, they're not useful. They won't tag what they're supposed to tag in the brain. Generally about a three hour window from the time that it is produced and transported to the site to actually be used. We measure that in Millicuries what is the radioactive level of the tracer. And when I had conversations about this and. I'm an early adopter, our local healthcare systems are now starting to do this. I said, here's another challenge. You're buying this tracer because that's how it works, and then you have to bill it out through those third party payers and one person doesn't show up For their scan, you just bought a very expensive tracer, or if they're late or, all kinds of logistical issues that are very complicated that really make the use of these PET based tracers impractical in my opinion. And I think, frankly, I've used them a lot because I do clinical research but if it hadn't been for the research and on the clinic side, the community side of my work. I don't use'em at all, quite frankly. But things did change, right? Things we have Lecanemab or LeqembI, Donanemab which is Kinsunla. They've both been approved last couple of years. And when those got approved, CMS finally came around and said, yeah, we're gonna pay for a PET scan at the beginning of treatment or to justify treatment. And that at about 18 months to make sure that we've cleared the amyloid as we should have with that is the pharmacological target of these treatments. Hopefully things really changed. And now again, we're in the age of blood-based biomarkers. So let's unpack what these tests are actually telling us. We hear terms like the amyloid beta 42 to 40 ratio. I mentioned P Tal 180 1 P Tal 2 17, or the percent P Tal 2 17. That's part of the productivity ad two test. Could you help our listeners understand what these biomarkers actually measure and how early in the disease process these biomarkers start to show their rear their head, so to speak and become something that's measurable and tangible and meaningful.

Dr. Rany Aburashed: 20:27

Yeah, I think that this is probably the most needed answer to question because I think a lot of clinicians ologists. Primary care physicians, doctors in general know very little about these biomarkers. The language around them sounds intimidating. And so I think, the way that I would unpack this is you look at amyloid 42, 40 ratios, right? Essentially to me that the way that I look at this is that's really the very first signal that there's a protein imbalance that, that's starting to shift in the brain, right? To me, a I view amyloid essentially as like the spark. You get this early deposition it can be decades before, and then when we see ratios change it is probably one of the earliest signs of Alzheimer's. And it sets the stage. Obviously it's an unstable protein, so it's not something that's easy to use as a screener. Because it's a challenge to do that blood test. You have to, the time matters to what you were saying earlier. The way you spin it down there's a few things that make that protein not as reliable as we'd like, but that's 42 40. When you look at tau and specifically PT, hyper phosphorylation of tau I think it's much more personal to an individual patient. And this to me is, 180 1 and 2 17 are the current big players? 2 17 is the one near and dear to my heart, obviously, but I think those are clear markers that are reflecting how the brain is responding to that amyloid stress. To me I view P Tal 2 17 as a molecular fingerprint of this entire disease process. It's incredibly sensitive to what's happening in the brain. A good indicator of tangles and inflammation and what we're seeing. Now when you get even more specific into the IV ad two test, you're looking at percent P Tal 2 17. I think we're really trying to quantify that signal and what they're doing is we're not no longer saying is tau present or not, but how much of it is abnormal? Compared to what's expected. So I think it gives a clinician a little bit of a readout that can help classify someone's risk. Is this someone you know showing no signs of pathology, someone in the early biological stages or someone. Already on that Alzheimer's continuum. The reality and the remarkable part of all of this is that this, these molecular changes are occurring often 10 to 15 years before the memory loss gets significant. At this stage prepared to say we should be testing asymptomatic many, the academic field is not ready to say that. but I do think we're headed that way. And I think that's gonna be the reality of where this ends up.

Dr. Ken Sharlin: 22:36

I agree and maybe a discussion for later, the most recent guidelines, the diagnostic guidelines. Do talk about identifying the neuropathological changes in folks who are asymptomatic. And what I really appreciated about those guidelines is of course you wouldn't diagnose somebody clinically as having Alzheimer's disease if they don't have the critical clinical features, the amnestic cognitive impairment, the loss of their instrumental activities of daily living. However, again, what I appreciated about it is that you can tell someone that they may be at risk, and I love saying at risk because at risk. It inherently implies action steps, right? It means, if you're at risk on the right, go to the left, right? You can do things about it potentially, that may significantly prevent you from ever getting Alzheimer's disease in the first place.

Dr. Rany Aburashed: 23:29

Yeah, absolutely. And when we talk about nerding a little bit later, I think I can highlight that as well, quite a bit.

Dr. Ken Sharlin: 23:35

That's great. So I know, just speaking as a clinician and of course you and I are specialists, but I get referrals from, the primary care arena and these tests are, and I'm talking now. Specifically about the tests that are ordered by physicians for their patients in their office. But we have LabCorp, we have Quest, we have privity. There's a couple other players out there with, using biological markers, some combining them together, some of them individually. And I think it must be very, confusing to folks, to our own colleagues about what they should be ordering and what is. Most clinically meaningful and even when to order them. And I, again, what we're talking about with Neurogen is a home-based test. It's a little different spin on the situation but our colleagues, I think, really don't have all the information that they ultimately need to provide a test to their patients. That gives them the most. Degree of the greatest degree of clinical accuracy.

Dr. Rany Aburashed: 24:36

I think in my discussions around the country as me and my team built urgent, it was incredible to see the gaps There's no uniform knowledge surrounding these biomarkers, you have pockets of people that are doing their own thing and trying to figure out, I think the first would say to a clinician is yourself, what are you trying to achieve with this test? And what I mean by that is, are you doing a top level screen where you're triaging, which is a lot of what we do at Neurogen, which is that sort of top of the funnel early, early flashing yellow light, so to speak for lack of a better term. are you trying to diagnose those two very different things? And so I think when you look at. A diagnosis of Alzheimer's based on the biomarkers. I think the closest we are to that, to a true confirmatory test outside of PET and CSF, it's probably, obviously we have the approval from from Fuji Rubio, and then we have and then I would say C2N's work is really strong. It's a strong test. The problem. Those tests are hard to scale. They're hard to scale. For two reasons. One, on the Fuji Rubio side, you have the instability of the protein of the P Tal 2 17 part is, okay. The other part is unstable and hard to really do it at scale. You have to really be a clinician who orders it and then has to be done at the right time in the lab. And then obviously mass spec, which is what C2N uses, is again, very challenging to scale, very hard to run in a high throughput way. So I would say to clinicians, if you wanted To really assess and start using biomarkers in a way that is meaningful to your patients. From the PCP standpoint, I would say the view there should be more triaging, right? Let's just see is this patient at an elevated risk? And to me, that's a simple pt, O2 17. That's what we offer at neuron at home. And that gives us that top of the funnel, right? We bring somebody in. get a flashing yellow light. Okay? There's something here. doesn't mean they have Alzheimer's, you don't make that diagnosis. Alzheimer's dementia is a dementia and all we're looking at is a blood test at this point. So there are patients that will end up with elevated PT 2 17 who don't go on to develop significant memory loss. So that flashing yellow light is where you start. And then I think you funnel people down into more detailed confirmatory testing, and that's how we built the ecosystem. But the reality is, when I initially started the company my idea was just do the at-home blood test. And then I realized very rapidly the bigger piece was the entire ecosystem, having every step of the network. In place for the education of patients and then also downstreaming after that, those high risk patients into brick and mortar neurology practices around the country with a Emerge and Diamond network where we knew those clinicians, would do confirmatory testing, would potentially get somebody in a trial potentially treat them. That's really been, I think, the holy grail and so that's how I approach it, it's prevention it's triaging and then it's confirmatory. And I think you have to order biomarkers based on what you're trying to assess.

Dr. Ken Sharlin: 27:19

And just for clarity sake, for folks, you're probably the strongest biomarkers are the P Tal biomarkers. Your some subtleties between 180 1 and 2 17. The amyloid 42 to 40 ratio informs that, but I wouldn't personally, as a clinician rely on that solely at all. And, I did want to bring up a couple other biological markers that, I think. Our colleagues will hear about and they've really been in use in clinical research for a long time and not exclusive to Alzheimer's. And that is Neurofilament light chain and glial fibrillary acidic protein or GFAP.'cause I do see them from time to time combined with the more specific biomarkers.

Dr. Rany Aburashed: 28:00

First of all, I love that you asked this question because my first exposure to biomarkers when I first started my research was neurofilament light. So that's the marker that I love and know very well. And so when you look at this, and you will see this, and clinicians will run across these two markers. So the way I would assess it in relation to Alzheimer's is I view Alzheimer's biomarkers as essentially an orchestra. And amyloid and P Tal 2 17, P Tal 180 1, those are definitely the lead instruments in the orchestra, right? They're providing the melody, the disease. Now Neurofilament light and GAP, I would consider them almost like the rhythm section in the background. They're telling us essentially how the whole brain is responding and what I would say is when you think of neurofilament light, so it's clearly a marker of neuronal injury. When you have stressed brain cells or cells that are breaking down, you start to increase your neurofilament light levels. The problem is it's really not specific at all, right? You see it elevated in. Variety of things. My research in it was in multiple sclerosis, a ton. But yes, it'll elevate in Alzheimer's, it'll elevate in ms. It'll elevate with traumatic brain injuries, normal aging. So there's a lot of caveats to using that. So you just have to use it in the context of, okay, I have, for example, elevated PT 2 17. In a patient with memory loss and we have some NFL changes maybe that's meaningful. Maybe it gives you a sense of the tempo of what's happening, right? How fast that damage is occurring. Now, gfap I think people know less about, so it's a, it's an astrocytic protein. And obviously astrocytes are, basically the support cells of the brain. So when you see an elevation of gfa I think it's really an early sign of inflammation or astroglia activation. It tends to rise even before Tau does in some patients, which means it might be one of the earliest warning lights, but again, non-specific and more supportive of stuff as opposed to the, P 2 17 is quite specific for Alzheimer's, whereas GFAP and NFL are much more broad based and elevate with a variety of other diseases. But I do think they're meaningful at interpreting the bigger picture. And eventually we'll get so good with them that we'll understand. What those ratios look like. how to use NFL as opposed to just a gut, reaction to an elevated level how to use it clinically, but it's exciting to be on this path. For me and probably for you, you're someone who's been in the functional health, really preventative care field of neurology. One of the few. It's exciting to at least know that. We're moving towards it, right?

Dr. Ken Sharlin: 30:13

See them as reflecting like the pace of neurodegeneration in the brain. So you will never want to use that as a sole diagnostic test. I will say I have used it very cautiously in very specific situations where there's really an absence of commercially available biomarkers. And I'm really broadly asking the question, are we dealing with a neurodegenerative process, for example? But I'm not. Depending on the result of the test to make a specific diagnosis, I already have to suspect that diagnosis. And here's another piece of the puzzle. Neurogen Biomarking, N-E-U-R-O-G-E-N, for those who wanna write it down Neurogen Biomarking, you, this is your company, this is your baby. You saw an opportunity to bring Alzheimer's testing out of the clinic. And into the home. And I'm wondering what inspired you to create this company and, what gap were you trying to fill?

Dr. Rany Aburashed: 31:10

Yep. so what happened is I was a hospital administrator and I practiced neurology. I've built neurology practice, I've done research. So for me, my entire career. I've broken into three buckets. My first one was true clinical, where I saw the pains of these diseases in everyday. People every single day. Built a very large practice with great partners that we did some amazing work and it's a great group still standing. then the research side with biomarkers became really my focus and my love. I still remember the first time I experienced and use, single molecule array technology. And I was like, this is the future of neurology. This is where we have to go. It's just the reality. And then on the hospital side I saw the reality, the throughput issues. I saw that for every 10 patients coming in from memory loss to a neurologist practice eight of them had had no neuro degeneration. It was polypharmacy, it was sleep apnea, it was, something that could have been handled at a PCP level. So what was happening was neurologists were just plugged with patients that really didn't need neurologists other than. A tap on the back and a couple of recommendations. So when the drugs came out, when we first got amyloid therapies, anti amyloid therapies I realized the uptake of these patients is very small. The number of People in the US that are treated is still, tiny. Compared to where, I'm not saying everyone should be on these agents but that meant that we weren't getting to them in time and they were coming to the neurologist way too late. So my first, the first problem I wanted to solve was, all right, how do we detect this disease as early as possible knowing that human behavior. that if I don't feel something, it's hard for me to consider doing anything about it. So you're dealing with human psychology where someone has minor symptoms. At this point we're not testing asymptomatic yet, but. young people have minor symptoms and you're trying to figure out how, when you actually can make a change in their disease, how do you get this blood test just to see if it's possibly something more. So that was the impetus for me to build the company. It morphed, into this. Incredible ecosystem. When I realized two things, I realized how many people wanted to know, which was incredible. people are dying to get our test. So I think 80, 80 some percent I think was the recent poll of people who would, who wanted to know. So people wanna know. And then the second part was how do you do this intelligently and. Ethically and in a scientific way where the rigor is extremely high. This is not a test in my eye that should just be flying off the shelves with no clinical. Infrastructure around it. I think it's dangerous. And so that's really where it came from. And so we started with the at-home kit. We were able to get that piece validated and approved. And we put some IP on that we have. And then we added the digital cognitive assessment because you wanted to know where these patients were. Was it, mild tic MCI, was it issues? It gave us a clinical picture. And then what we did was, the most important piece was put the telehealth neurologists as our educators. We went with a telehealth board certified neurology team that we educated on the markers they have to pass through our network to even be allowed to provide this information to patients.'cause they have to understand the nuance of the test. Do you have kidney disease? Have you had a recent stroke? Have you had a heart attack? Do you have any cancer? All these things can affect your P Tal level. So what ended up happening is really a beautiful system and I remember when we did our first 200 people through the system we had about 20% positive rate. And I sat in and listened to those patients that with the neurologist and I sat like a fly on the wall. I just wanted to see and it was something out of a movie to me. Again, I can't even explain it. were people who were still in the workforce. They were handling their finances, they were having some memory issues, and they were covering, their brains were covering and they were early, And we caught them early. Now these were actionable patients. And that's when I, that was that eureka moment when I finished, I remember like we, as a team. I was like, they were like, why are you so emotional? I was like, this legitimately changes the entire scope of how we approach Alzheimer's. This is gonna change how Alzheimer's is treated, how we manage it, at scale. It's been a labor of absolute love. I didn't set out to do it. All I wanted to do was, not have P Tal 2 17, which is a great screening test, sit on the for 10 years while people argue and put it on PowerPoint slides that's what I wanted.

COMMERCIAL BREAK: 35:07

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Dr. Ken Sharlin: 36:50

Walk us through this very practically. Who's the ideal user? What does the journey look like? How, from the moment maybe I'm the right person to be doing this task, to I order it to, I ship it somewhere, and what happens?

Dr. Rany Aburashed: 37:04

Yeah, so it's a lot of infrastructure, I'll tell you that. It was not easy to build this, it's, it sound, I make it sound very simple, but there's a lot of pieces to the puzzle. But essentially number one, we needed it to be consumer directed. So we wanted people to be able to request it. We wanted the people who had some concerns about their loved one's memories or their own memories. To be able to start somewhere, like just start here. And I want you to think about rural Iowa. I want you to think about the middle of Montana, right? you and I, our physicians, we can find the best physicians. They're friends they're a text message away. you and I, but most people can't do that. That's not a luxury most people have. you come to the website, you order the kit, there's a series of questions that we ask. We don't test people under the age of 40, so it's 40 and above. If you have a direct family history of early Alzheimer's, so 40 to 50. You have to have some, indication within your direct family of early Alzheimer's and you have to have memory loss, some type of memory, subjective or objective memory loss. And then it's 50 and over with subjective cognitive issues. So we ask a series of questions that sort of assess cognition and all of that information then goes to our neurology team and they either approve or don't approve the test. So we have a checkpoint there at the beginning because what we don't want is an 18-year-old doing this test or a 30-year-old who we know is gonna that's just stealing people's money. So we just said to heck with that, and we're not doing that. So it's the right patient non one. Then with and then they get a kit to their home. The blood test is done at home at your convenience. It's, the idea here is we know you're probably still working. We know you probably have kids, or you may have children or that are in college or maybe high school, late high school. And we know your life is busy. And we know that if we don't make this as easy as possible for you, it's unlikely it's gonna happen. If I have to make you go to a lab or go to your doctor, it's gonna just decrease the number of people we catch. They then have a portal where they do their digital cognitive assessment. Takes about seven to nine minutes, depending on the patient, gives us a really good indicator of, top level where they are cognitively. And then all that information comes together. Now we do have a central clia, ccle cap certified lab for the whole country. So New York included where we do all our testing in Houston and everything goes there. but the beauty of it is, we've. democratized this innovation. it can be done in the middle of Iowa. They have a telehealth neurologist with them from wherever who can guide them. And they might have to drive a few hours if they're positive, but we at least have found them early and we tell them where they need to drive to. So this is where we recommend you go now. And so we hand that off. And then the clinicians make their final decisions, obviously at the brick and mortar practices.

Dr. Ken Sharlin: 39:28

There's a lot of sort of prequalification. We're very careful. We, there's a lot of communication that has to happen because to your point, you could test positive for a biological marker. You may never get the disease itself. In a pretty early, phase of your subjective cognitive decline. In my practice, but I'm very cautious about communicating.'cause the last thing I want somebody to do is get a positive test for Alzheimer's disease and jump off the top of the tallest building in town. And I think, of course not to take anything away from Neurogen or any other company in the biomarker business, but we, I think both of us would like to emphasize that. Even not everybody that tests positive for biological markers ultimately develops the disease. So definitely want to partner with an expert, and be able to understand in context what's going on, and then really embrace the belief that there are a lot of options for, especially, today and hopefully even more moving forward with things. I am curious about this network and how folks are informed of their results and how they're triaged from there. You've touched on it a little bit. And our mutual colleague Barbara Pickett who I think works very closely with you on this have discussed it, but I think folks really need to understand what that looks like.

Dr. Rany Aburashed: 40:49

Yeah so what we've done is we've basically divided the country up into quadrants. And within each quadrant, we partner with what we're, with, what with what we have is, which is a urgent and diamond network. Soner and Diamond network practices, our practices that we assess for capabilities for innovation in Alzheimer's. Meaning that there are practices that have to meet certain criteria. that can be, clinical trial access, that can be disease, modifying therapy, access PET scan access. They have to be, so and so we've, we basically break the country down geographically, and we have pockets, and now we're expanding it even further. So obviously as we scale the company, it will go. Right now it's pocketed, within quadrants, people might have to drive targeting bigger cities, targeting, but what we also look at, for example, in Oklahoma, let's say we get orders from 200 miles 200 mile, radius in Oklahoma. Where's our, where is the, where is there a practice or two that are at least on the cutting edge or innovative enough to consider therapy if they see the right MCI, early ad patient? Who tests positive, on PET imaging, confirmatory testing, which is really where it goes. That's one of the bottlenecks that we are seeing is we have this slew of positive patients that we are getting into practices and PET scan access is very limited around the country. and we're now starting to tackle that as well. We just said we have to solve this problem too. And so as a company, we're looking at how can we bolster that as, how can we do PET scans around the country to get confirmatory testing in a way that's controlled? Is it, is know direct where we actually have freestanding PET scan units strategically placed around the country? the reality with that is you invest in that. And are we steps away from one of these blood-based biomarkers knocking PET off and not, PET not being required. I don't know if we're gonna get there soon, but eventually we will. I think.

Dr. Ken Sharlin: 42:35

Oh I very much think so. I've had that conversation with C2N and, I authored a couple papers with them and, one conversation was, I was still doing lumbar punctures, and they said, do you think you're gonna get to the point where you're just gonna use this in-office blood-based biomarker tests? And I said I love the test, but gosh, I don't know that I would rely on it a hundred percent. Fast forward to, November 2025. And yeah, I have access to PET scan. But the test is incredibly useful and I do find it completely validating and for the most part it's made PET in my clinical practice. I won't say obsolete, but unnecessary for the most part. So it's been great. Great.

Dr. Rany Aburashed: 43:19

I would agree with that. And one of the things for me is the way that I view how I believe Alzheimer's how we should approach this as an Alzheimer's neurology committee. I believe very heavily in C2N in us, in our triaging of patients. I would love all of them, the positive ones to go into to, to, and get confirmatory with C2N. To me, that's the pathway that I believe we need. And the reason I believe that is I think it's a great test. I just think. gotta get the right patient. It's not cheap. Our entry point is very easy. And now imagine us funneling all the right people. To C2N the, instead of a hundred people, 80 of which are gonna be P Tau 2 17 negative anyways Now you have those 20 people that are positive going and getting, a much more detailed biomarker analysis with C2N. And at a fraction of the cost we started and then we were able to, and now that allows us to go to the 40 million people. We're trying to target the 40 million Americans with memory loss over the age of 45 or 50 who don't know what it's from. So we're able to get a look under the hood at the top level and then funnel things down. But I'm very excited to see where we go as a community in this state. I don't think we should be, I don't look at them as comPETitive. I look at the opposite actually. I think C2N is a phenomenal test. It's just not something that you can do at scale. It's just expensive.

Dr. Ken Sharlin: 44:31

And I, again, correct me if I'm wrong, this was just a previous discussion with Dr. Pickett, but that your test can be done in a way that's anonymous. Is that correct?

Dr. Rany Aburashed: 44:41

So because we are consumer directed, it is the consumer's debt. So one of the things that people don't realize is that biomarkers are not protected, like genetic testing is under Gina. When you look at insurance companies and what they might do long term, so there are some ethical concerns surrounding this data and obviously there are teams working at the governmental level to get this information protected, so you can't be biased versus people who have an elevated P 2 17 in terms of insurance and so on and so forth. And it is the patient's information. So we leave it to the patient. Even if the patient agrees to be referred to a neurologist, if they're elevated and we recommend neurology and they say, yes, I want to go see neurology, the patient has to disclose the lab test to the neurologist. The neurology team knows that they're, it's a neuron patient coming, so they probably know it's an elevated PT, O2 17. But we don't put that in the chart for patients purposefully. We want the patients to be empowered and in control of their health. And we have to be thinking about the governmental side of it and the protections that are needed for citizens when it comes to this stuff, because it can get really scary if you do a blood test. That predicts a disease in 15 years, for example, eventually what does that mean for you and your ability to be treated, equal as a citizen?

Dr. Ken Sharlin: 45:51

And now there may be some neurologists who are listening to this podcast. if they wanted to become involved.'cause I'm sure you need, there just aren't enough of us, in my town, you could wait. Months to years to get into a neurologist. How can neurologists become part of your network?

Dr. Rany Aburashed: 46:08

Yeah, it's a great question. So we are proactively now building out neurology practice, building out that the urgent and diamond team. So we are proactively reaching out to neurologists, explaining what's going on well, welcoming them, asking if they wanna come in. A lot of them are academic partners now but we're doing it with private practices now too, that have you. Robust practices that run a really good neurology. And we want more. We want as many as we can get. The first step that I would say is on the website, you can email our support team and we'll reach out right away. So if you're interested or you're somewhere in the country, we need your help. The reality is You get a real neurology patient, you have a patient at your doorstep it's not gonna be managing depression and pseudo dementia. It's gonna be someone that you gotta work up, that may have disease. And I think most neurologists, that's what they want to do. We want to practice neurology. We want to take care of people that have neurological illnesses. And instead of seeing 10 patients, two of which may have a neurodegenerative condition in a day, you might see 10 actual neurodegenerative patients where you can impact their life in a very meaningful way. I'm very proud to say proof of concept for us has been incredible. So we have been able to get people from end to end. And many of them now, there's a landslide of people going on disease modifying therapy. Our screening tests They ended up getting into a neurologist practice one of our diamond network practices, and then they're even developing their own neuron within the practice. Now, where an NP might see the patient first at intake. get some cognitive assessments, whatever they use, and then they're immediately getting pat done and then they follow up with the physician. And they're ready for treatment potentially. So it's it's really been fun to watch the practices respond as well.'cause a lot of the practices are like, this is a great pathway for us. This brings us the right neurology and those patients even. And the reality is the system needs these patients. Long term as well. Neurologists want to follow their patients. They, you gotta, they're running a business as well, so it, if there's no margin to a neurology practice, there's no mission. So you, you have to, and so obviously getting people on treatment, infusion chairs are being filled. There's PET imaging there, there are reimbursable events that occur to get these patients in.

Dr. Ken Sharlin: 48:06

And the other piece of it that I'm very passionate about, is there were a handful of us out there who believe that most of the diseases we deal with, including Alzheimer's or. Largely preventable. That there's a huge impact of diet, lifestyle, and environment. And you have people like Rich Isaacson out there calls himself a preventative neurologist. He's trained another doctor out there who says she's the first. Fellowship trained preventative neurologists. Part of my practice is preventative neurology and it's a wonderful thing to see, especially when we contract things using biological markers to actually show that the action steps that are being taken are making a big dent in those neuro. Pathological changes in the brain. And so I'm wondering is, do you see this at least if not now, hopefully in the next five or 10 years as this, interest in lifestyle medicine and systems biology really takes off that your tests will be a centerpiece for a lot of that.

Dr. Rany Aburashed: 49:07

I think it's gonna be a massive flashing yellow light for people. And to your point, we know the lifestyle modification changes and how powerful they are in the Alzheimer's world, right? We also know the vascular risk modification. And if you actually tackle that aggressively and appropriately. Even if you have Alzheimer's, it slows it down substantially because obviously blood flow matters significantly. That's why exercise helps so much. And so I think to your point we're entering into, a new era on healthcare where it's digital health, it's precision health, it's individual health. Each person's measuring their metrics every day. And understands. The effects of exercise on their heart rate or the effects of their sleep and so on and so forth. And I think we're gonna do the same thing in neurology. So there is an entire burgeoning field coming of longevity and prevention, which I think is not pseudoscience. I think it's very much needed and scientifically based. So I'm very excited to see that piece come up as well.'cause we would love to feed these people into that and get them. That's the best treatment we can give anybody

Dr. Ken Sharlin: 50:05

Oh yeah. And obviously a subject for several more podcasts, but I want to just seed that a little bit for folks who are maybe taking a few notes or are gonna look at the show notes. This morning I was reviewing some of the data that's come out from what's called the Finger Study looking at the huge impact particularly of optimizing Omega-3 fatty acids in the brain, both from a cognitive perspective as well as literally growing new brain tissue, expanding cortical thickness and so forth as a result of optimizing these Omega-3 fatty acids. Other things being important be vitamins also and some antioxidants. And I'm not telling people to go out and take a bunch of supplements. I'm just saying they're. Definitely are things out there that can be done. And then hand in hand with that, recently reviewed a lot of the data coming out from your city of Chicago, the super ages, data from Northwestern University as profound. And really shows that even if you have an A POE four gene, and you may even have. Those neuropathological changes in your brain that a percentage of individuals will actually resist developing the clinical disease. So tremendous amount of hope out there.

Dr. Rany Aburashed: 51:23

Very exciting. It's a fun time to be in the thick of my career. I like where I am in my career because of where the science is right now.'cause I feel like there's so many opportunities for us to leave an imprint that can help. People and we're starting to feel that in Alzheimer's much like we did in multiple sclerosis in 2010 when Gilenya came out. Leading uP Tau Ocrevus and B-cell therapy. So it's an exciting time I think for all, for neurologists.

Dr. Ken Sharlin: 51:46

Dr. Aburashed, it is really inspiring to spend time with you. How you're setting an example of science and technology and compassion and bringing them all together to truly help folks out there who are in need. I truly appreciate everything you've done and spending the time with us on a Healthy Brain Toolbox podcast.

Dr. Rany Aburashed: 52:07

That was fantastic. thank you so much for the thoughtful questions. It was great. Appreciate it.

COMMERCIAL BREAK: 52:14

Hi everyone. Dr. Ken Sharlin here with the Healthy Brain Toolbox. I'd love to hear from you. If you have general questions about brain health, neurology, or the science of keeping your brain sharp. Send them to questions@healthybraintoolbox.com. I'll be reading your questions on the upcoming episodes. Please remember, these need to be general questions, can't answer personal medical questions, or provide individual medical advice. So if you've ever wondered about brain health strategies, lifestyle tips, new research, or the future of neuroscience, send those questions in. I look forward to hearing from you and who knows? You might even hear your question featured on the show. Thank you for tuning into the Healthy Brain Toolbox podcast. I hope today's conversation gave you new insights to protect and nourish your brain. Be sure to subscribe, leave a review and share this episode with anyone looking to take control of their health. Until next time, stay sharp and keep learning.