In this YouTube presentation, MD‑PhD neuroscientist Dr. Nick Norwitz walks viewers through a newly published Cell paper that demonstrates a surprising link between cancer and Alzheimer’s disease. Using multiple mouse models of Alzheimer’s, the researchers implanted lung, colon, and prostate tumors and observed a dramatic reduction in amyloid plaque burden across several brain regions. They then showed that the effect is mediated not by the tumor mass but by proteins secreted from the cancers; administration of these cancer‑secreted proteins to tumor‑free Alzheimer’s mice also lowered amyloid and rescued performance on standard memory tests (Morris Water Maze, Y‑maze). Proteomic analysis pinpointed cystatin C as the key secreted factor. Human cystatin C binds amyloid, promotes its degradation, and activates brain immune cells to clear plaques, leading to restored cognition when administered daily for 30 days in mice. Dr. Norwitz emphasizes that these findings are still basic‑science and not yet translatable to humans, raising questions about blood‑brain barrier delivery, timing, and safety. He then pivots to evidence‑backed, personally used interventions for cognitive longevity: (1) lysophosphatidylcholine‑DHA (LPC‑DHA) – a brain‑targeted omega‑3 formulation (Eccentrate Omega Max) that raises brain DHA more effectively than standard fish oil; (2) low‑dose lithium orotate (≈5 mg daily, Pure Encapsulations) which inhibits GSK‑3β, reduces amyloid/tau pathology, and has epidemiological support; (3) NAD⁺ boosting strategies, including aerobic/resistance exercise, ketogenic diets, fasting, and supplementation with nicotinamide mononucleotide (NMN) or nicotinamide riboside (NR) at 1 g daily, shown to double NAD⁺ levels in humans. The talk concludes with a call to stay curious, skeptical, and rigorous while acknowledging the dramatic but still preliminary nature of the cancer‑Alzheimer’s connection.
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Are you ready for this? One of the world's top science journals just dropped a biological plot twist no one saw coming. Cancer might kill Alzheimer's disease. If I were to sum that up in a facial expression, it would be— Right? Okay. Now, if you're new here, let me introduce myself. My name is Nick Norwitz. I'm an MD-PhD neuroscientist who also happens to be high risk for Alzheimer's disease, so I spend a lot of time overturning stones to find out what might help protect my brain for the long term. And this research discovery, I couldn't have imagined it in my wildest dreams. Cancer and Alzheimer's are two of the most feared diseases, and in this research, they violently collide in a way that might reveal new paths to treatment. So today I'm going to show you the data. I'm going to walk you through the graphs, show you what the researchers did, what they found, and how it all boils down to one protein they think explains it. Then we're gonna zoom out and I'm gonna share a concise set of evidence-backed things I personally do today to protect my brain for the long term. And don't worry, none of them involve getting cancer. You ready for this? Let's go. So basically, this is an exciting and thought-provoking development, and the results were shocking. And they landed on a single key player known as— have significantly lower incidence of Alzheimer's disease. What in the broader cocktail, the broader soup, was actually responsible for reducing amyloid? Exactly why? We stay curious. So first, a roadmap. This video has just two main parts. In part one, we're going to review these new data showing how cancer-secreted proteins, one in particular, fights Alzheimer's disease and what it might mean. And then in part two, I'm going to provide a high-yield review of supplements for cognitive longevity and Alzheimer's prevention, things I do myself. As always, you can find more research, all the deep dives, at staycuriousmetabolism.com. I'll link everything below. I also want to warn you up front: I want to show, not just tell you about the data, so I'm going to walk you through some graphs that might be intimidating, but I respect your intelligence enough to try. You just have to try with me, okay? Ready? So, this new paper was just published in Cell, one of the top 3 science journals in the world. Now, for a bit of background, there have been prior epidemiological human population studies that have hinted that people with cancer or a history of cancer have significantly lower incidence of Alzheimer's disease. I'd heard that before in medical school, but like many, I dismissed it and just waved it away because, yeah, cancer kills people, and if you're dead, you're not going to get Alzheimer's disease, right? But it turns out it's more complex than that. Biology is humbling us. That's always fun. So the researchers here, they started with animal models because they wanted to show a causal cascade. Importantly, They didn't just test one cancer type, they tested many, starting with three: lung, colon, and prostate cancer. In mice predisposed to Alzheimer's disease, they implanted them with any of these cancers, then examined their brains, focusing on amyloid, a core pathological feature of Alzheimer's disease. And the results were shocking. Now get ready, I actually want to show you the graphs because I believe you can understand it. In all three cancer groups, across multiple brain regions, including the cortex, the more evolved region, the thalamus, the dentate gyrus, important in memory, and the basolateral amygdala, important in the limbic system and emotion, consistently the mice with cancer had markedly reduced amyloid plaque levels in their brain. You can see that here in the primary data, the red and green staining images of the brain, and in the bar graphs that quantify those levels. So the red is the control Alzheimer's mouse, and the other colors are Alzheimer's mice with cancer—much lower amyloid levels. But of course, we don't want to get cancer to avoid Alzheimer's disease. That's like chopping your toe clean off to avoid a hangnail. It fixes one problem but creates another problem. So the next big question is, is it the cancer itself or something that the cancer is secreting that could be hijacked? So to find out, the researchers isolated cancer-secreted proteins—that's exactly what it sounds like, proteins secreted from cancers—and they gave these to Alzheimer's mice, but these mice didn't have tumors, didn't have cancers, and the same result. Cancer-secreted protein treatment reduced amyloid in the brain. This alone is fascinating. It means it's not the tumor mass causing changes, it's something secreted by the cancer that's affecting the brain. Okay. Now, if you're following, you might be thinking, "Okay, that's cool. Amyloid reduction. It's interesting. But do these cancer-secreted proteins actually improve cognition and memory? Because that's really what matters, right?" So this is where things get really interesting. Using multiple different validated memory tests, like the Morris Water Maze Test or the Y Maze Test, standard tests for memory in mice, the researchers found that mice treated with the cancer-secreted proteins had improved learning and memory. Great Scott! I'm going to show you a graph. Now, I know this looks chaotic, but it's not that hard to understand. These are data from what's known as a Morris Water Maze Test, In this test, mice are placed in a little pool with milky water so they can't see through the water, and they need to learn and remember the location of an escape platform, which is in the top left quadrant. And then in subsequent trials, the amount of time the mice spend in the correct quadrant is a measure of memory. Animals treated with the cancer-secreted proteins performed better on this and other memory tests. So, to quote the authors, They say, "Together, these findings indicate that cancer-secreted proteins released from multiple cancer cell types, but not the physical burden of the peripheral tumor itself, inhibits amyloid pathology and can rescue cognition in a preclinical mouse model of Alzheimer's disease." That is really cool if you truly understand it. But the researchers didn't stop there. They wanted to to pinpoint which component of these cancer-secreted proteins was responsible for the anti-amyloid effect. What in the broader cocktail, the broader soup, was actually responsible for reducing amyloid? And they landed on a single key player known as cystatin C. Notably, cystatin C is elevated in human patients across a wide range of cancers, helping to build a case for human relevance. Digging even deeper, the researchers showed that human cystatin C directly binds to amyloid and promotes its degradation. So once again, quoting the authors so you can hear it from the horse's mouth, cystatin C secreted by cancer cells is essential for the degradation of pre-existing amyloid plaques in the brain. But again, the researchers didn't stop there. I know, I sound like a broken record, but it's exciting. So to test whether cystatin C could have therapeutic potential, The researchers purified human cystatin C and then injected it into Alzheimer's mice once daily for 30 days. And the results were really cool. The injected cystatin C localized with immune cells in the brain right around amyloid aggregates. And they didn't just sit there. Basically, the cystatin C activated those immune cells, powering them up to break down and clear out plaques. So simply put, Stepping back, this specific cancer-secreted protein, cystatin C, helps the brain's immune cells power up and clear out harmful toxic amyloid. And the most exciting part: this treatment didn't just affect brain pathology, the amyloid, it reversed learning and memory deficits in Alzheimer's animals. That is truly incredible. Now, there are more mechanistic details, and you can check those out in the Stay Curious newsletter linked below. I'll also highlight that we now have a collected list of deep dives specifically on Alzheimer's disease for those of you ambitious enough to want to become neuro experts. So check that out below. But I realize I've been asking a lot of your attention, and I'm grateful you've stuck with me thus far. And I do want to get to some practicals as well. But I do want to be clear and caveat. At present, these findings we just discussed, they're breaking new basic science. So they're an important piece of the evolving puzzle on Alzheimer's disease, but the clinical utility is still limited. I can't give you concise practical takeaways from this research because I also don't want you to just have to get cancer to boost cystatin C. So there are open questions that remain and need to be answered. For example, could human cystatin C or analogs across the blood-brain barrier actually be developed into effective treatments for Alzheimer's? And if so, how early will we need to intervene in humans to have a meaningful effect? Also, obviously, what are the potential off-target or un— foreseen side effects that manipulating this pathway could cause in human beings. So basically, this is an exciting and thought-provoking development, part of the scientific process that is ever-evolving and, done right, never truly finished. So I hope you found these data as fascinating as I did, because I think what we just walked through captures exactly why we stay curious. It's that sense of biological wonder, biological elegance, that keeps this work, this field, thrilling. And that I think is deeply human. But with that, let's pivot a little bit so I can share some practical evidence-based tools and interventions that I use to protect my brain from Alzheimer's. Of note, each one of these comes with its own deep dive breakdown, which I'll link below. But let's get on to it. Number 1, this is a big word, brace for it, lysophosphatidylcholine DHA. The brain absolutely relies on omega-3s. Including and especially the long-chain omega-3 DHA. This is arguably the most important nutrient for brain health, making up 40% of the fatty acids in the brain's gray matter, and it has a multitude of structural and signaling properties. So for many, consuming dietary sources of long-chain omega-3s, particularly DHA, primarily fatty fish like sardines and salmon, will be sufficient to support long-term brain health. However, for others, like me, who are at high genetic risk for Alzheimer's disease or dementia, there may be added advantages of consuming a special form of DHA called lysophosphatidylcholine DHA, or LPC-DHA for short. This form has privileged access to the brain through a particular transporter, and it's significantly more effective at raising brain DHA levels, which you can see here in orange, as compared to conventional fish oil, which is in red, which tends to concentrate more in fat tissue. Now, I reviewed these data on lysophosphatidylcholine DHA and brain metabolism in deep dives that I've linked below, but to disclose the product I use personally and intend to take for many years to come, it's called Eccentrate Omega Max. It contains a patented form of highly concentrated lysophosphatidylcholine DHA. Warning, it is not cheap, but for me and my parents and those who really want to invest in protecting their brain if you're at high risk of Alzheimer's disease, I think it's a worthwhile investment. I do have a discount code for you, Stay Curious for 20% off. Now, I'm not a 91 pills per day biohacker kind of guy like some, but I do believe in this product, and for those with the means and motivation, it's something to consider. But moving on. Next up on our brain roster is a deceptively simple element, lithium. Despite its small size and relative atomic simplicity, it plays a powerful role in brain health. Now, earlier research suggested an association between higher trace lithium levels in drinking water and lower risk of Alzheimer's disease. But earlier on, this was just an association. Newer data show a strong biological rationale for how lithium might exert its neuroprotective effects. One thing lithium does is it inhibits a protein called GSK3 beta. This protein— you don't need to remember its name— but it's involved in key processes in Alzheimer's disease development, including promoting amyloid plaques and the development of phospho-tau neurofibrillary tangles, which sit inside neurons and basically choke them to death. As well as brain insulin resistance. Interestingly, when you examine human brains too, lithium levels are reduced in the cortices of patients with cognitive impairment and Alzheimer's disease. And even more interesting, lithium appears to be sequestered by the pathologies of Alzheimer's itself, like amyloid plaques. So it gets trapped in the amyloid plaques when it's needed for brain health. And if you're paying attention, you can see how this sets up a vicious cycle: lower lithium, more GSK-3 beta activity, which leads to more amyloid and tau pathology, which means more lithium sequestration and thus lower lithium availability, and the cycle continues and continues. And to add to this story, in a headline-grabbing study published out of Harvard last year, researchers show that lithium deficiency can cause Alzheimer's pathology in animal models, and that supplementing with a specific form of lithium, specifically lithium orotate at very low doses— this is not treating bipolar disorder here— at very low doses could reverse those pathologies. You can see this video for a deep dive. But the overall body of evidence has led me to personally supplement with low-dose lithium, microdosing at 5mg of lithium orotate daily. The brand I use is Pure Encapsulations, as a disclosure. This is a well-established and reputable company. I have no affiliations. It's just what I use myself. Now, moving on. 3. NAD stands for nicotinamide adenine dinucleotide. Again, no quiz. But rounding out our high-yield hit list is NAD. NAD is a critical energy-carrying molecule in the brain. It's kind of like ATP but different. But it sits at the center of nearly every major metabolic process: glycolysis, beta-oxidation, oxidative phosphorylation, the Krebs cycle, TCA cycle, and more. You don't need to know those either. But without NAD, this is the point, there is no energy, there is no life. And interestingly, Alzheimer's disease is characterized by a deficiency of NAD+. Or to frame it another way, NAD+ is a resilience factor for the aging brain. NAD+ levels naturally decline with age, but studies show that when NAD+ levels remain elevated, cognitive function is preserved even in brains with significant Alzheimer's pathology. So in other words, high NAD+ may buffer against brain neurodegenerative changes. And the good news is NAD levels can be boosted that are very modifiable regardless of age. Proven strategies to boost NAD include aerobic and resistance training, trying to build up muscle, improve VO2 max, ketogenic diets, and fasting. And for those exploring supplementation, there are NAD precursors that in human randomized controlled trials have been shown to boost NAD, including nicotinamide mononucleotide and nicotinamide riboside. You can really use either. And the human RCTs show that supplementing with 1 gram daily of either NMN or NR can double NAD+ levels in as little as a couple weeks. So for a deeper dive on those data, check out the content linked below. So now, closing. Science rarely hands us plot twists this dramatic, where two of the most feared diseases, cancer and Alzheimer's, collide in a way that feels to me almost mythic. This singular study won't change Alzheimer's treatment tomorrow, but it might change how we think about Alzheimer's today. And that shift in mindset is often how real breakthroughs begin. From here, our challenge, my challenge to you, my challenge to myself, is to stay rigorous, stay skeptical, and above all, stay curious.
