Why Don’t We have a Cure for Alzheimer’s Disease Yet?

Are you caring for a loved one with dementia? You don't have to figure this out all on your own. Welcome to Truth, Lies Alzheimer's, the show that helps you reimagine a new relationship with your loved one, a relationship a little more free of stress and anxiety. Join host Lisa Skinner and her 30+ years of experience as she guides you on a new path to a better relationship with those you care for. Here's Lisa.

Hello everybody. Welcome to another new episode of The Truth, Lies Alzheimer's Show. I'm Lisa Skinner, your host. How many of you have been asking yourself, why don't we have a cure for Alzheimer's disease? I can tell you honestly, I've been asking myself that for decades, and I stumbled across this really interesting article in a publication called The Conversation. Um, this was actually published March 18th, 2021, and the author's name is Donald Weaver. He is a professor of chemistry and the director of Cranbill Research Institute at the University Health Network at the University of Toronto. And he actually addresses that million-dollar question. I want to share that with you today. It's really fascinating. So as a researcher, he's saying this as a researcher. Who studies Alzheimer's disease and a neurologist who cares for people with Alzheimer's disease, he shares in the frustration, indeed anger, of people and families when he tells them that he has no cure to offer. Over the past year, scientists have tackled COVID-19, which was a previously unknown disease, but within months they were able to develop effective new vaccines, which we all know. Over that same timeframe, the list of Alzheimer's treatment failures got longer. Currently, the only approved drugs for Alzheimer's merely alleviate some of the symptoms, partially and temporarily, but do not stop the disease from progressing. Although it was first officially described— we're talking about Alzheimer's disease— 115 years ago, and of course, we know that it existed long before that, we still do not have a cure. For this devastating disease. Why? Well, let's start by following the money. For years, patient advocates have pointed to the escalating toll and ballooning costs of Alzheimer's as the world's population ages. Alzheimer's is severely underfunded in comparison to cancer, heart disease, HIV and AIDS, and even COVID-19. Just as a side thought, I want to mention that a few years ago I took a course through the Alzheimer's Association, and that question came up. Why don't we have a cure for Alzheimer's disease? And the woman from the Alzheimer's Association gave me the exact same, or gave us in the course, the exact same answer that this gentleman is giving you. It's due to lack of funding and why these other conditions have just excelled in research over Alzheimer's disease. So to me, that's consistent with what this gentleman is saying. Sadly, The mistaken belief that Alzheimer's only affects older people is a contributing factor to this underfunding. However, 5 to 10% of people with Alzheimer's are under the age of 65. Some are even in their 40s. Alzheimer's is also a disease of the entire family, causing anxiety, depression, and exhaustion in caregivers. Nothing that we don't know, right? And of course our loved ones, exacting a disproportionately high socioeconomic cost. There are conflicting theories, and funding is not the only issue here. The human brain is extremely complex, And Alzheimer's disease is the most complex disease of the brain. The challenges that arise from this collision of complexities are reflected by the many competing theories of Alzheimer's disease. We still don't know what causes it. The most time-honored theory is that Alzheimer's is caused by misfolded proteins that aggregate or clump which as a result kill brain cells and give rise to the symptoms of memory loss and reduced cognition. Initially, the culprit in this misfolding story was a protein, and we've all heard this, called beta amyloid. More recently, another protein, tau, has emerged as a possible contributor. Now, although a wealth of research data have supported this protein misfolding theory referred to as the amyloid hypothesis, multiple drugs designed to block the brain's toxic protein misfolding processes have failed in human trials repeatedly. In fact, in the past 2 years, several major clinical trials based on the field's leading hypothesis, which is the amyloid hypothesis, is that reducing the level of aggregated beta amyloid that riddles the brains of Alzheimer's patients would halt disease progression have dramatically failed. And this kind of reminds me of a couple studies that I've told you about in the past. Uh, the first one was the Nun Study, and what they found upon doing autopsies on the brains of people who were in the trial, that some of these women, the nuns that participated in the trial, upon their death in the autopsies, some of these nuns were found to have these plaques and tangles in their brains, but they showed absolutely no symptoms of dementia. And conversely, some of the people who were symptomatic and showed extreme symptoms of dementia during their life, which progressed. When they did the autopsies, there were no plaques and tangles. And I've always wondered, how do you explain that? I think this article is explaining that away for us today. That might not necessarily be the only cause of Alzheimer's disease, is with these plaques and tangles that we call proteins, the amyloid hypothesis, in other words. And so there are actually many other theories. A new heavyweight contender is the neuroinflammation theory of Alzheimer's, which suggests that the disease arises from an excessive release of toxic inflammatory chemicals from immune cells in the brain called microglia. This is a new theory. I've read about this before. Drugs designed to address this theory are fundamentally different from those addressing the amyloid hypothesis, but they're still early in the developmental process. A different theory claims that Alzheimer's disease is the disease of synapses. Which are the junctions between brain cells. And yet another suggests that Alzheimer's disease is a disease of mitochondria, a structure, cell, central to energy production in every brain cell. And I have been reading about this theory recently. So this is another theory that is being researched. So, obviously, this in part are challenges to finding a cure. The path towards a cure is not going to be easy. And even if these theories do lead to the development of drugs, these drugs may fail for a host of other reasons. One of them is that Alzheimer's disease can present for many years before the symptoms even begin. Alzheimer's is a very long chronic disease. And from what scientists are able to tell, that they're probably present 20 to 30 years before the first symptoms become obvious. Giving the drug when a person becomes symptomatic may be too late for it to make any difference. This is consistent with the other research information that I have found to be true. But we do not have the ability to diagnose it 30 years before the first symptoms appear. And even if we could, We would need to consider the ethics of giving a potentially toxic drug long-term to someone who may or may not develop the disease in 3 decades. Also, unlike developing antibiotics in which the researchers know within days if the drug works, the chronic nature of Alzheimer's requires long, expensive trials years in duration before an answer can even be attained. Such time and expense is a further impediment to drug development. One final problem is that Alzheimer's may not simply be just one disease. It may actually, in fact, be a collection of similar diseases. For example, a 52-year-old with early onset Alzheimer's certainly has a clinical course distinct and different from an 82-year-old with late onset Alzheimer's disease. The question is, will a drug that works in an 82-year-old also work in a 52-year-old person's disease? Maybe, but maybe not. These are all questions that have not been answered yet. But thankfully, despite these many hurdles, a wealth of fascinating and encouraging research is taking place in laboratories around the world. The successes of science and the pharmaceutical industry against many other diseases over the past century have often arisen from picking low-hanging fruit. Alzheimer's disease is not a low-hanging fruit, but the apple at the very top of the tree. And scientists are going to have to climb a lot of branches, many of which have never been trodden upon, on the way to a cure. But he feels confident that we will eventually get there. I thought that was a fascinating, fascinating article about some of the theories as to why we still have not yet found a cure for Alzheimer's disease. Now, this gentleman, Donald Weaver, again, he's the professor of chemistry and director of the Krembill Research Institute. At the University Health Network at the University of Toronto. This was also published in The Conversation on September 19th, 2022. And the question here is that he's going to answer for us, I'm sharing with you, is that Alzheimer's might not be primarily a brain disease. A new theory suggests that it's an autoimmune condition. And I thought you all would find this to be equally as fascinating as the last article he wrote. I do. So I want to share it with you. The pursuit of a cure for Alzheimer's disease is becoming an increasingly competitive and contentious quest, with recent years witnessing several important controversies. In July of 2022, Science magazine reported that a key 2006 research paper published in the prestigious journal called Nature identified a subtype of brain protein called beta amyloid as the cause of Alzheimer's, which may have been based on fabricated data. This is the amyloid hypothesis that I was just talking about and the current theory of what causes Alzheimer's disease, the plaques and tangles that form in the brain that kill the brain cells. However, and he goes on to say, one year earlier in June of 2021, As we've heard, the US Food and Drug Administration had approved the drug aducanumab, an antibody targeting beta amyloid, as a treatment for Alzheimer's, even though the data supporting it were incomplete and contradictory. Some physicians believed aducanumab never should have been approved. While others maintain it should have been given a chance. This is the one that the FDA withdrew their approval of. With millions of people needing an effective treatment, why are researchers still fumbling in this quest for a cure for what is arguably one of the most important diseases confronting humankind? Well, that's certainly something I want to know. We need to escape the beta amyloid rut, he says. For years, scientists have been focused on trying to come up with new treatments for Alzheimer's by preventing the formation of brain-damaging clumps of this mysterious protein called beta amyloid. In fact, as scientists, we have arguably got ourselves into a bit of an intellectual rut concentrating almost exclusively on this approach, often neglecting or even ignoring other possible explanations. And let me remind you, because I recently said this in one of our other episodes, that the new drugs, the ones that are actually being used to treat people with Alzheimer's disease that are administered intravenously, that don't break— completely break the blood-brain barrier, those are completely focused on the plaques and tangles, the proteins. And supposedly they're believed to go in and clear them out, but the results are not living up to the expectations that they thought. So this is very consistent with that, uh, current theory. Regrettably, this dedication to studying the abnormal protein clumps has not translated into a useful drug or therapy. The need for a new out-of-the-clump way of thinking about Alzheimer's disease is emerging as a top priority in brain science. The laboratory that he works in at the Krembil Brain Institute, which is part of the University Health Network in Toronto, is devising a new theory of Alzheimer's disease. And this is based on their past 30 years of research. And what they're starting to believe is that they no longer think that Alzheimer's is primarily a disease of the brain. Rather, they believe, or starting to believe, that Alzheimer's is principally a disorder of the immune system within the brain. The immune system, found in every organ in our bodies, is a collection of cells and molecules that work in harmony to help repair injuries and protect from foreign invaders. So, for example, when a person trips and falls, their immune system helps to mend the damaged tissues. When someone experiences a viral or bacterial infection, The immune system helps in the fight against these microbial invaders. Well, from what they're discovering, these exact same processes are present in our brains. When there is head trauma, the brain's immune system kicks into gear to help repair it. When bacteria are present in the brain, our immune system is there to fight back. So the new theory that they're continuing to research and explore is that maybe Alzheimer's is an autoimmune disease. They believe that beta amyloid is not an abnormally produced protein, but rather is a normally occurring molecule that is part of the brain's immune system. It's supposed to be there. When brain trauma occurs or when bacteria are present in the brain, these beta amyloid proteins is a key contributor to the brain's comprehensive immune response. However, this is where the problem begins, according to Donald Weaver. Because of striking similarities between the fat molecules that make up both the membranes of bacteria and the membranes of brain cells, beta amyloid can't tell the difference between invading bacteria and host brain cells. And the result is that they mistakenly attack the very brain cells that it's supposed to be protecting. I find that to be an incredibly interesting theory. So the bottom line is that it leads to chronic progressive loss of brain cell function, which ultimately culminates in dementia, all because our body's immune system cannot differentiate between bacteria and brain cells. When regarded as a misdirected attack by the brain's immune system on the very organ it's supposed to be defending, Alzheimer's disease emerges as an autoimmune disease. There are many types of autoimmune diseases. We've heard of most of these. Rheumatoid arthritis, in which autoantibodies play a crucial role in the development of the disease. And for which steroid-based therapies can be effective. But these therapies will not work against Alzheimer's disease. The brain is a very special and distinctive organ, recognized as the most complex structure in the universe. In our model of Alzheimer's, beta amyloid helps to protect and bolster our immune system. But unfortunately, it also plays a central role in the autoimmune process that they believe may lead to the development of Alzheimer's disease. Though drugs conventionally used in the treatment of autoimmune diseases may not work against Alzheimer's, they strongly believe that targeting other immune-regulating pathways in the brain will lead us to new and effective treatment approaches for the disease. Now, some other theories of the disease include, in addition to the autoimmune theory of Alzheimer's, there are new and varied theories that are beginning to appear. For example, some scientists believe that Alzheimer's is a disease of tiny cellular structures called mitochondria, the energy factories in every brain cell. Mitochondria convert oxygen from the air we breathe and glucose from the food we eat into the energy required for remembering and thinking. Some maintain that this is the end result of a particular brain infection. With bacteria from the mouth often being suggested as the culprit. Still others suggest that the disease may arise from an abnormal handling of metals within the brain, possibly zinc, copper, or iron. It is gratifying to see new thinking about this old-age disease. Dementia currently affects more than 50 million people worldwide. With a new diagnosis being made every 3 seconds. Those are the most current statistics today that are expected to triple by the year 2050. That's pretty scary. Often people living with Alzheimer's disease are unable to recognize their own children or even their spouses of more than 50 years. There's no question in any of our minds that Alzheimer's is a public crisis in need of innovative ideas and fresh directions for the well-being of the people and families living with dementia and for the socioeconomic impact of our already stressed healthcare system Coping with the ever escalating costs and demands of dementia. We need a better understanding of Alzheimer's, its causes, and what we can do to treat it and to help the people and the families who are living with it. Folks, we know that tsunami of Alzheimer's disease is clearly on its way. And to me, the information that's contained in these two articles that I just shared with you almost seems like we're starting back at square one. But the point is, we still don't know, even know what causes Alzheimer's disease. The theory they've been working on for decades is maybe proving to not be the case. And the new drugs that have been approved by the FDA to clear out these plaques and tangles aren't showing significant changes in people's cognitive decline. I think that's pretty profound. So maybe some of these are— these other theories are in part what's actually contributing to the cause of Alzheimer's disease. But we still don't know. But I thought you'd all find this very interesting information. I certainly do. But it's also really disheartening to think that we still don't have a clue, and we have a long, long way to go. But time is catching up with us. Because I've said before, according to the Alzheimer's Association and the World Health Organization, our number of people who are projected to develop Alzheimer's disease by the year 2050, which do the math, it's 25 years away, is expected to triple worldwide. And we are nowhere near being prepared for the number of people and the impact it's going to have on our society until at least a treatment, if not a cure, is found. So that's kind of the way things stand today. It's not real encouraging. It's encouraging that they're discovering some of these new theories, but I don't know. Makes me feel like, okay, back to square one. I guess we'll have to wait and see. But I'll keep bringing you this information as I come upon it because it's very interesting and fascinating. And I think all of you have a right to know the most current information that's available about Alzheimer's disease, especially those of us, including me, whose lives have severely been impacted by this disease. We either care for people living with Alzheimer's disease, or we have loved ones. It's in our families, and we're dealing with this day in and day out over a very long course that it takes for the disease to progress to the end. So thanks for being here with me again today. I appreciate your time. I hope you find this information valuable. I'm not trying to burst anybody's bubble or discourage anybody, but I think it's important that we know what the truth is about everything that's discovered about this disease. So please come back next week for another new episode of The Truth, Lies Alzheimer's Show with me. I'm Lisa Skinner, your host. Take care. Have a great rest of your week, and I'll look forward to having you back next week. Take care for now. Bye-bye.

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