Dr. Rudolph Tanzi is a titan in the field of neurogenetics, where his groundbreaking research is reshaping our understanding of Alzheimer’s disease. As the Director of the Genetics and Aging Research Unit at Massachusetts General Hospital, Co-Director of the McCance Center for Brain Health and the Joseph P. and Rose F. Kennedy Professor of Neurology at Harvard Medical School, he’s at the forefront of innovative Alzheimer’s research. His pioneering work includes the discovery of all three early-onset familial Alzheimer’s disease genes and the creation of the revolutionary “Alzheimer’s-in-a-Dish“ model, which has catalyzed drug discovery for Alzheimer’s treatment. With his relentless pursuit of knowledge and novel treatments, Tanzi is a true game-changer, inspiring hope in the face of a devastating disease.
Beyond his groundbreaking scientific contributions, Dr. Tanzi is also a New York Times bestselling author, co-authoring international bestsellers like “Super Brain“, “Super Genes“, and “The Healing Self” with Dr. Deepak Chopra. His unique ability to distill complex scientific concepts into accessible narratives has made these works invaluable resources for those seeking to understand the intricacies of the mind and health. Tanzi’s multifaceted brilliance – as a scientist, author, and communicator – continues to illuminate our path towards understanding and overcoming Alzheimer’s disease.
In this interview, I speak to Dr. Rudolph Tanzi, one of the world’s foremost experts on Alzheimer’s disease and brain health. Our discussion navigates the terrain of brain evolution as we age, delving deep into the triggers, diagnosis methods, and potential remedies for Alzheimer’s disease. We shine a light on the groundbreaking research and promising therapies that hold the potential to mitigate the havoc wrought by this debilitating illness. Our exploration is a beacon of hope, illuminating the path towards a future less burdened by this devastating disease.
Q: How do our brains change as we age?
[Prof. Rudolph Tanzi]: Let’s explore the topic of how experiences shape our brains. Our brains consist of about 100 billion nerve cells and neurons, with a potential for making anywhere from tens to hundreds of trillions, some even say a quadrillion, connections known as synapses. Due to a phenomenon known as neuroplasticity, our neural network continually restructures itself. Each time we learn something new or encounter a fresh experience, we trigger a reconfiguration of our brains. I’ve delved into this fascinating concept in my book, “Superbrain,” aimed at a lay audience interested in neuroplasticity.
As we age, two key changes occur. Firstly, we tend to become more set in our ways. The capacity for neuroplasticity remains, but our increasing rigidity, typified by phrases such as “my way or the highway,” leads to a decline in this brain flexibility. Neuroplasticity is highest during youth, explaining why children and young adults up to the age of 25 absorb knowledge so rapidly. Their learning capacity is immense, akin to sponges soaking up water.
However, as we grow older, this changes slightly. Despite the continued potential for neuroplasticity, people tend to cling to the familiar for a sense of security. This results in fewer new synapses forming, while existing synapses strengthen. I strive to resist this natural progression as a scientist, aiming to maintain a flexible, plastic brain rather than allowing the same synapses to continually fire.
Next, we need to address age-related diseases affecting the brain. Alzheimer’s disease, for instance, involves the formation of amyloid plaques, sticky substances that accumulate outside nerve cells. Within these cells, you’ll find tangles that choke their interiors. These plaques trigger the tangles’ formation, resulting in nerve cell death and instigating a process of inflammation—neuro-inflammation in this context. This inflammation exacerbates the issue, killing ten times more nerve cells.
The concerning fact is that this pathological process occurs in nearly everyone as they age. Post 40, many individuals start developing plaques, tangles, and inflammation. The progression to Alzheimer’s disease can span anywhere from 10 to 30 years. It involves the formation and spread of amyloid plaques and tangles throughout the brain, inducing inflammation along the way. This inflammation is the major contributor to cell death. Eventually, significant loss of nerve cells and synapses leads to cognitive decline. This process represents the most common age-related brain change, leading, in this case, to Alzheimer’s disease.
Q: What is the scale of Alzheimer’s in the population?
[Prof. Rudolph Tanzi]: In the United States, it’s estimated that around 7 million people are living with Alzheimer’s disease. One critical issue I constantly emphasize is our late diagnosis of Alzheimer’s. The disease is typically identified once the brain has already suffered significant deterioration and dysfunction. If we were to compare this to our approach with heart disease, it’s like only making a diagnosis when a coronary bypass is needed. Similarly, with diabetes, we wouldn’t wait until half the beta cells in the pancreas have been lost before making a diagnosis.
Alzheimer’s starts its destructive process 30 years prior to its typical diagnosis. Therefore, when considering the prevalence of this disease, we’re speaking of 7 million diagnosed patients in the US. But then, one might ask, how many Americans currently have the initial stages of Alzheimer’s, characterized by amyloid plaques, cell death, tangles, and inflammation, already festering in their brains? I concur with the higher estimates, suggesting around 40 million people.
To effectively combat Alzheimer’s, we need to adopt the same early detection strategies used for other age-related diseases like heart disease, diabetes, and stroke. Our aim should be to identify the changes before the organ has deteriorated to the point of significant dysfunction, making it challenging to restore its health. This proactive approach is our path forward.
Q: What is the curent diagnostic paradigm for Alzheimer’s?
[Prof. Rudolph Tanzi]: Our pipeline of discovery is constantly improving, enabling us to identify early signs of Alzheimer’s disease through brain imaging. These techniques can reveal if there is Alzheimer’s pathology developing in your brain that might lead to cognitive symptoms in one to three decades. While brain imaging, specifically PET scans for amyloid and tangles, is indeed effective, it can also be costly.
Thankfully, several companies are now developing blood tests, making detection more accessible and affordable. These blood tests can provide insights into what’s happening within the brain. For instance, a company in St. Louis called C2N, along with other technologies like Lumipulse, can identify the formation of amyloid plaques or tangles in the brain by analyzing a blood sample.
In the future, these kinds of blood tests will become commonplace. They will allow us to offer treatments for Alzheimer’s disease 10, 20, or even 30 years before symptoms start to manifest, much like how we currently handle cholesterol. Nowadays, we can detect high cholesterol levels through a blood test, enabling individuals to take cholesterol-lowering medication or make lifestyle adjustments, or both, to prevent heart disease. This early detection and intervention will be our strategy for combating Alzheimer’s.
Q: How can we treat Alzheimer’s?
[Prof. Rudolph Tanzi]: …we do possess treatments capable of removing amyloid from the brain, which is the good news. However, the less positive aspect is that these treatments are incredibly costly and come with significant safety concerns. They are immunotherapies, involving the intravenous injection of antibodies against amyloid. After being introduced into the bloodstream, some of these antibodies penetrate the brain, attach to the amyloid plaque, and signal nearby cells to consume and eliminate it. These therapies are quite effective in clearing the amyloid.
However, there are some major drawbacks. The cost of these immunotherapies, whether from BioGen, Eisai or other companies, falls between $25,000 and $30,000 per year. Moreover, these therapies may lead to swelling in the brain and hemorrhaging, requiring six MRIs if you’re on the drug for a year to monitor amyloid levels, escalating the total annual cost per patient to about $100,000.
If we consider the United States, where potentially 40 million people could discover through brain imaging or blood tests that they have amyloid in their brains, the question arises: how can healthcare systems afford to provide a $100,000 per year therapy to so many people? It’s simply not feasible.
The next step, therefore, is to develop small molecules, or little white pills, that can perform the same function in a more cost-effective and safer manner. This precise line of development is the focus of my research.
Q: What is the toll of Alzheimer’s on the individual experiencing the disease?
[Prof. Rudolph Tanzi]: Surveys show that, surprisingly, more people fear Alzheimer’s disease more than they do cancer. This is due to the fact that Alzheimer’s isn’t a quick affliction; it extends over a period of 8-20 years, during which individuals slowly lose themselves. This disease methodically dismantles your neural network, a network that represents a tapestry of experiences and connections you’ve built throughout your life. These include experiences at school, with family, loved ones, children, and spouse.
Who you are, how you perceive yourself, and how others perceive you, all are enmeshed within this tapestry, which consists of billions of neuronal connections. Alzheimer’s, in essence, pulls this tapestry apart, thread by thread. Initially, the loss is subtle but terrifying: forgetting names, leaving a running car in the garage, neglecting a stove-top meal. These small lapses are frustrating and frightening, and as the disease progresses, these symptoms worsen, leading to agitation, fear, and eventual withdrawal. You find yourself unable to follow conversations, struggling to find words, and eventually, failing to recognize your own loved ones. The disease’s trajectory is heart-wrenching.
Once patients reach these advanced stages, caregiving responsibilities typically fall to the spouse or children. It’s an emotional burden. Imagine parents who have just seen their children off to college, looking forward to their retirement, only to find themselves caring for their own ailing parents—often avoiding institutional care.
Compounding the problem, two-thirds of Alzheimer’s patients are women, and the majority of caregivers are also women. This means that the disease disproportionately affects women, not only as patients but also as caregivers. So, in multiple ways, females bear the brunt of Alzheimer’s more than males do.
Q: Where should philanthropists direct their capital in the fight against Alzheimer’s?
[Prof. Rudolph Tanzi]: Consider the various Alzheimer’s foundations as a guide to choose your focus. For instance, the Alzheimer’s Association, the largest foundation in the US, primarily focuses on caregiving. They offer respite for families and guidance for those dealing with newly diagnosed patients. They also lobby in Washington to increase funds for research.
If your interest is more towards funding intensive lab-based research, there are other organizations. While the Alzheimer’s Association does fund research, foundations like Cure Alzheimer’s Fund and Bright Focus are renowned for supporting high-impact research globally. Cure Alzheimer’s Fund, for instance, supports our Alzheimer’s Genome Project. I started this project when discovering the first Alzheimer’s genes during my early academic years.
Choosing a foundation can depend on whether you want your donation to directly aid families or to fund groundbreaking research. Websites like Charity Navigator can help evaluate the effectiveness of these foundations. Cure Alzheimer’s Fund, for example, is a top-tier charity because every dollar donated goes directly into research without any deduction for overheads, a cost borne by the founders and board members. They disburse about $25 million annually in research funding.
The decision for philanthropists is about what they care the most about. Some lean towards funding visionary basic research that will have significant implications in the next 10-20 years. Others opt to fund ongoing clinical trials that pharmaceutical companies might overlook. For example, in our research, we screen existing drugs and natural products to identify treatments already available at the pharmacy that could work. Previously, this was painstaking as each experiment using mouse models of Alzheimer’s took two years.
However, in 2014, our lab developed an “Alzheimer’s in a dish” concept—mini human brain organoids that show early pathology to disease symptoms within just 6 weeks, mimicking a 30-year process in humans. According to a Nature article we published, this approach should accelerate drug discovery by tenfold and make it ten times cheaper, but in fact, it has made it a hundred times faster and cheaper.
[Vikas: Brains in a dish?!]
[Prof. Rudolph Tanzi]: Yeah, it’s crazy. They make synapses, they talk to each other, like what the hell are they talking about, they’re little pea sized brains. And we put the glial cells in and we can see them clean up the amyloid, and then we can piss them off and they become inflammatory and kill everybody. It’s crazy. We keep making them so much better. We’ve got a new paper in press in neuroscience, where we added a blood brain barrier and like peripheral blood cells coming into it, interacting and we joke, we say if we keep making this thing better and better we’ll probably have to give it benefits.
Already, we’re seeing new patentable drug combinations emerging from this approach. For instance, Amylyx, a company I co-founded and hold equity in, has had success with a new drug for ALS developed from repurposed existing drugs. It’s now a public company valued at $2 billion on NASDAQ. This breakthrough is largely due to our approach of using organoid systems for quick screening, combining known drugs to create new treatments. Following this line of research, I’ve started a new company, Acta Pharmaceuticals, to make drug discovery even faster by creating new combinations of existing treatments.
Q: What can we all do, as individuals to improve our brains and prevent disease?
[Prof. Rudolph Tanzi]: As the co-director of the McCance Centre for Brain Health at Massachusetts General Hospital, our main goal is to educate and advise patients on disease prevention and brain health maintenance. In pursuit of this, I’ve written several books. In my latest work, “The Healing Self,” I summarize advice on preserving and promoting brain health through an acronym: SHIELD.
The ‘S’ in SHIELD stands for Sleep. During sleep, your brain naturally expels amyloid plaque and reduces inflammation. ‘H’ is for Handling Stress. By managing your stress through methods like meditation or adjusting expectations, you can combat inflammation.
‘I’ represents Interaction. By engaging with others, you expand your neural network and bolster your cognitive resilience. ‘E’ is for Exercise. Regular physical activity not only clears out amyloid plaque but also stimulates the birth of new nerve cells, particularly in the brain areas most affected by Alzheimer’s.
‘L’ signifies Learning New Things. This fosters the formation of new synapses, which in turn builds your cognitive reserves. I often tell those nearing retirement not only to consider their financial reserves but also their cognitive reserves. You need to make new synapses daily, especially as you age, due to the inevitable synaptic loss through inflammation.
Lastly, ‘D’ stands for Diet. Undoubtedly, the Mediterranean diet, particularly plant-based with plenty of fibre, nuts, seeds, fruits, whole grains, and vegetables, is the best for brain health. The reason being that it benefits your gut microbiome.
We’ve published numerous studies showing the crucial role your gut microbiome plays in maintaining a healthy brain. Your gut is home to trillions of bacteria from thousands of different strains. Keeping them content assists in amyloid plaque removal from your brain and inflammation reduction. While some people rely on probiotics, that’s not enough as they only supply a small fraction of the bacterial diversity your gut needs. Instead, it’s more beneficial to nourish them properly, which is achieved through a fibre-rich, plant-based diet. By keeping your gut bacteria happy, you keep your brain healthy, which is why the Mediterranean diet is the best choice for brain health.
Neuroplasticity and epigenetics, combined, play a crucial role in reducing inflammation. It’s important to remember that inflammation is the primary culprit behind many diseases, both in the brain and throughout the body. The lifestyle advice I often impart is centered around preventing inflammation, which is key to maintaining good health.
Think of it this way – various factors can spark inflammation in our bodies, much like lighting a match. For instance, in Alzheimer’s, amyloid plaques are one of these matches, and tangles can be compared to small brush fires. But these alone won’t lead to the disease, just as matches and brush fires alone won’t cause a forest fire. What truly wreaks havoc is when these isolated issues combine and escalate into a full-blown forest fire, which is inflammation in this analogy. As we age, we may encounter more of these matches and small fires, but if we can prevent them from becoming a forest fire, we remain healthy. The goal is to keep inflammation at bay.
It’s simple, really. Drink plenty of water, prioritize sleep, and be mindful of your diet. These are areas where people often err – not sleeping enough and consuming unhealthy food. For instance, coming from a family with a history of obesity, I’ve adopted a vegetarian diet since my college days and avoid overeating to maintain a healthy weight. If I consumed three full meals a day like most people, I’d struggle with my weight, so I stick to a plant-based diet with occasional dairy products.
Avoid processed and junk foods. Stay clear of meat, particularly hormone-laden chicken. If you do eat fish, avoid fatty varieties, as they tend to accumulate harmful substances like cesium, lead, mercury, and cadmium due to the pollution in our oceans. Opt for leaner fish instead. Don’t smoke, keep your blood pressure in check, and moderate your alcohol consumption. Adopting these lifestyle choices can greatly contribute to your overall well-being.
Q: What do you hope your legacy will be?
[Prof. Rudolph Tanzi]: In addition to my scientific endeavors, I also have a passion for music. I played all the keyboards on the latest Aerosmith album, and similarly, contributed to Joe Perry’s most recent work. Perry, Aerosmith’s guitarist and co-founder alongside Steven Tyler, once imparted wisdom that I find parallels science quite fittingly.
In Perry’s words, a musician should never dwell on what’s already been played or continually revisit past performances. Instead, they should always maintain the conviction that their best show is yet to come. In this light, I don’t believe in legacies or resting on past laurels.
To me, what truly matters is the firm belief that you haven’t yet reached your peak – that your best work is still ahead, regardless of your age. This mindset doesn’t just apply to music but also to science and, in fact, any endeavor. It’s what keeps your mind sharp and your motivation high.
You shouldn’t just sit back and marvel at your past achievements. That’s the past. Instead, you should always strive for improvement, aiming to outdo yourself in the future. In short, take a page from Joe Perry’s book and always believe that your best performance is still to come.