In this presentation Dr. David Perlmutter examines a recent post‑mortem study titled “Adult Hippocampal Neurogenesis Is Abundant in Neurologically Healthy Subjects and Drops Sharply in Patients with Alzheimer’s Disease.” He explains that adult neurogenesis occurs primarily in the dentate gyrus of the hippocampus, a region critical for memory and heavily affected in Alzheimer’s disease. The study compared 45 brains (ages 52‑97) with Alzheimer’s pathology, ranking them by Braak stage (1‑6), a microscopic measure of neurofibrillary‑tangle burden. Results showed a steep inverse relationship: higher Braak stages (more tangles) corresponded to dramatically fewer newly generated neurons. Notably, reductions in neurogenesis were detectable at early Braak stages, before widespread tangle accumulation, suggesting loss of neurogenesis is an early event in disease progression. Perlmutter argues that restoring hippocampal neurogenesis could be a therapeutic avenue. He outlines practical, BDNF‑mediated strategies to boost neurogenesis—regular aerobic exercise, coffee‑fruit extract, turmeric, DHA, and a ketogenic diet that raises β‑hydroxybutyrate. The talk concludes that enhancing neurogenesis may help slow or prevent Alzheimer’s pathology.
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Well, hello everyone. I'm Dr. David Perlmutter. A lot that I've been talking about over the past couple years has looked at the relationship between something called neurogenesis, the growth of new brain cells, and Alzheimer's disease. We've talked about how we as humans retain the ability to grow new brain cells in various parts of the brain, and specifically in an area called the hippocampus. To be more specific, in an area called the dentate gyrus of the hippocampus. That'll become important in a moment. But I have to say that we have not had a huge amount of literature that has necessarily correlated neurogenesis or lack of neurogenesis, lack of repopulating the brain with new cells, with Alzheimer's disease. In the new study that we'll look at in just a moment, This correlation was made really quite substantially. These researchers looked at the rate of neurogenesis and were able to compare it to the accumulation or not in the brain of something called neurofibrillary tangles. Neurofibrillary tangles are something seen in the brain that the pathologist can look at postmortem that does relate to Alzheimer's disease. Let's just go ahead and take a look at the study. This is a very interesting study, and it's called Adult Hippocampal Neurogenesis Is Abundant in Neurologically Healthy Subjects and Drops Sharply in Patients with Alzheimer's Disease. Even from the title, it suggests that growth of new brain cells is seen in individuals who are neurologically intact but not seen in individuals with Alzheimer's disease. We know Bullet point 1, that the hippocampus is the area of the brain that has a pivotal role in memory, and that's one of the most affected areas in Alzheimer's disease, as you might expect. We also learned that adult hippocampal neurogenesis, the growth of new brain cells in this memory center, confers protection, if you will, to the hippocampus. We know that there are a robust number of new brain cells developing in our brains virtually all of our lifetimes. In this study, they studied people up until their 9th decade. It doesn't mean it doesn't continue. Other research tells us it continues even later than that. But as they state in sharp contrast, the number and the maturation— in other words, developing into fully formed neurons— of these neurons progressively declined as markers of Alzheimer's disease advanced. And so let's take a look at the study. They looked at a group of individuals. They looked at their brains, rather. These are individuals who died for whatever reason, 45 people with Alzheimer's disease aged 52 to 97, and they wanted to Rank these patients with Alzheimer's disease in terms of the severity of their diseases at the time of their death. And they did, bullet point 2, rank them by what are called the Braak stages, stages 1 through 6. The highest level means the highest level in the brain of neurofibrillary tangles. That's something seen with the microscope. More of those and the more distributed as relates to this study, they are throughout the brain, the higher is the Braak stage. In other words, this is a way of determining from a pathological perspective the degree of Alzheimer's disease. Now let's take a look at this chart. What this shows us is really quite interesting. High Braak stage 6 that you see here listed in red correlates with a very low number of new brain cells. Less neurogenesis corresponds to higher levels of those neurofibrillary tangles, markers of Alzheimer's in the brain. It'll get a lot easier for you at the— in the next slide. And what this is showing us is in the control patient— or not patient, individual— these are looking at markers of new brain cells being Distributed in the hippocampus. These green triangles mark these areas that are stained to show new brain cells. Now, if we look at the Braak stage 6, what do we see? As you can appreciate, a dramatic reduction in the growth of new brain cells. So neurogenesis is reduced. In lockstep with the degree of Braak stage. Now again, Braak stage is a marker of severity of Alzheimer's disease based upon the findings in the brain of the distribution of these neurofibrillary tangles. Notably, alterations in adult hippocampal growth of new brain cells, neurogenesis, were detected at early stages of the disease, even before the generalized presence of these tangles was seen. In other words, the loss of the growth of new brain cells is an early finding, and moreover, what they're asking us to consider is that therapeutic strategies aimed at increasing the number and functionality of these cells might be relevant to prevent or slow down Alzheimer's disease progression. What can we do to increase the number and functionality of these new brain cells. In other words, how can we augment neurogenesis? We will talk about that in just a moment. Of note, our results demonstrate a profound multifaceted impairment of the growth of new brain cells, neurogenesis, in the hippocampus in patients with Alzheimer's, starting at early stages of the condition. Therefore, restoration of normal levels of hippocampal neurogenesis, the growth of new brain cells, If we can restore that in these patients, that emerges as a potential therapeutic approach to counteract the progression of this as yet incurable disease. Well, this is a very interesting study, isn't it? It looks at the relationship between higher levels of neurogenesis and lower levels of those pathological changes in the brain that we call neurofibrillary tangles. This makes this connection, I think, very, very more supported, especially when you think about the commentary of the authors. The take-home message, or at least question, would be if neurogenesis does relate to reduced collection in the brain of neurofibrillary tangles in some way, or let's just say neurogenesis, growing new brain cells, is important, what can we do to make that happen? Well, neurogenesis is controlled by many factors, one of which is BDNF, brain-derived neurotrophic factor. So raising BDNF augments neurogenesis, and that seems like it's a good idea. How do you raise BDNF? One of the simplest things is to exercise. Spending 20 minutes a day doing some kind of aerobic exercise, great, you'll feel better. But really, really good for your brain, enhancing BDNF, turning on neurogenesis. Other things, a whole coffee fruit extract or concentrate that we see now at the health food store, even turmeric and DHA, and a ketogenic diet. Who knew ketones, specifically one rather, beta-hydroxybutyrate, a byproduct of getting into ketosis, one of the ketone bodies. has been shown to augment the production of BDNF and as such give you a leg up on neurogenesis. Today we learned about a powerful relationship between neurogenesis and Alzheimer's disease. Thank you for listening. I'm Dr. David Perlmutter. Bye for now.
