Alzheimer’s Disease: Are We Close To Finding A Cure
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Medical News Today
In the US, around 5 million people aged 65 and over are living with Alzheimer’s, the majority of whom are women. This number is expected to almost triple to 16 million by 2050.
First described in 1906 by Dr. Alois Alzheimer, Alzheimer’s disease is the most common form of dementia, accounting for around 60-80% of cases. It is characterized by problems with memory, thinking and behavior.
Onset is most common in individuals aged 65 and over, although people in their 40s and 50s can develop what is classed as early-onset Alzheimer’s.
Alzheimer’s is a progressive disease, meaning memory loss is mild in the beginning, but it worsens over time to the extent that individuals are unable to have conversations or respond to their surroundings.
There are treatments that have been approved by the US Food and Drug Administration for Alzheimer’s. For example, cholinesterase inhibitors and memantine can help treat memory and thinking problems. But these drugs just help manage the symptoms there is currently no cure for the disease.
In the US, around 5 million people aged 65 and over are living with Alzheimer’s, the majority of whom are women. This number is expected to almost triple to 16 million by 2050. Figures are similar worldwide by 2050, more than 115 million people are expected to have the disease.
Jelly Drops: An Exciting New Invention To Help Combat Dehydration In Dementia
Inspired by his grandmother, Lewis Hornby has invented bite-sized sweets known as Jelly Drops to help reduce dehydration in dementia.Alzheimers Society was delighted to partner with Lewis and the Jelly Drops team this year through our Accelerator programme. Together, we’re working on bringing their fantastic product to people living with dementia.
Q: First The Bad News Why Have All Drugs Tested In The Past Several Years Failed
In retrospect, the idea that reducing amyloid in the brainwhich all the failed drugs dois based on an incomplete picture of the disease.
To treat a disease, we need to treat whats broken. But its very difficult to find whats broken in these slowly progressive brain disorders.
One way to find whats broken is through genetics, but the first wave of genetic studies in the 80s and 90s only had the technical capabilities to investigate Alzheimers cases that run in families, those caused by a single gene.
The results of these studies all seemed to converge on one biological process: amyloid.
But these single-gene forms of Alzheimers are rareand account for maybe 2% to 3% of cases. Most cases of Alzheimers are caused by a complex interplay of many genes and the environment.
The field made the assumption that amyloid is the primary culprit in all forms of Alzheimers. It made perfect sense, because we see amyloid in all patients with Alzheimers, whether their disease is caused by a single gene or not. The amyloid finding was extremely exciting, and there was a sense that we were on the cusp of curing this devastating, horrible disease.
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Will A Treatment For Alzheimers Ever Be Found
In the 90s, Alzheimers researchers were full of optimism. New genetic studies all pointed to one culprithard clumps of protein, called amyloid, that litter the brains of people with the disease.
With the emergence of the first tangible target, pharmaceutical companies jumped in to develop drugs to clear amyloid from the brain. In animals, the drugs appeared to improve memory. But the results of human clinical trials that followed were disheartening: One after one, these drugsall designed to target amyloidhave failed to slow the disease.
The onslaught of news about these failures has left the public wondering whether amyloid has anything to do with Alzheimersand whether a new approach is needed.
The field has already begun to redirect its focus, says Scott Small, MD, director of Columbias Alzheimers Disease Research Center and the Boris and Rose Katz Professor of Neurology at Columbia University Vagelos College of Physicians and Surgeons.
Theres now reason to be cautiously optimismistic, he says, because we have uncovered new pathways that lead to the disease, and we know that they truly make a difference.
The CUIMC Newsroom spoke with Small about the current state of research into Alzheimers treatments and prevention.
Why Dementia Is So Hard To Treat
Despite the vast number of people affected globally, with an estimated 46.8 million people currently living with dementia, there is currently no cure. While current treatments manage symptoms they offer no prospect of recovery.
Part of the difficulty in finding treatments for dementia stems from the fact its not a single disease, but a complex health problem with more than 50 underlying causes. Dementia can be better thought of as an umbrella term describing a range of conditions that cause parts of the brain to deteriorate progressively.
Most drug treatments currently in development have targeted the pathology of Alzheimers disease, the most common form of dementia, which accounts for about 60 to 70% of all cases.
Finding a successful treatment for Alzheimers faces two major hurdles: the first being we still dont know enough about the diseases underlying biology. For example, we dont know what exactly regulates the toxic build-up of amyloid- plaques and tau tangles in the brain that are found in Alzheimers patients, which specific types of these are toxic, or why the disease progresses at different rates in different people.
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The Devastation Of Alzheimers Disease
With all this said, we are extremely aware of the gradual and cumulative devastation that Alzheimers disease causes, as patients lose their memory and cognitive functioning over time. In late-stage disease, people can no longer hold a conversation or respond to their environment. On average, a person with Alzheimers disease lives four to eight years after diagnosis, but some patients can live up to 20 years with the disease.
The need for treatments is urgent: right now, more than 6 million Americans are living with Alzheimers disease and this number is expected to grow as the population ages. Alzheimer’s is the sixth leading cause of death in the United States.
Although the Aduhelm data are complicated with respect to its clinical benefits, FDA has determined that there is substantial evidence that Aduhelm reduces amyloid beta plaques in the brain and that the reduction in these plaques is reasonably likely to predict important benefits to patients. As a result of FDAs approval of Aduhelm, patients with Alzheimers disease have an important and critical new treatment to help combat this disease.
The Difficulty Of Diagnosis
Because Alzheimers disease has a wide array of causes, symptoms can vary tremendously from person to person.
For Diane, one unexpected symptom was hallucinations. She began seeing visions of her husband and seeing images of her two daughters as young children.
Alzheimers presents itself differently in every single person, said Chris Riley. Theres some very general things that can happen, but when people have Alzheimers, each persons experience is unique to themselves.
This makes a clinical diagnosis, or a diagnosis off the basis of symptoms, tricky.
The clinical diagnosis of Alzheimers disease by a physician due to his experience in the area is usually right but not always, said Dr. Victor Henderson, professor of health research and policy and of neurology and neurological sciences at Stanford University, and director of the Stanford Alzheimers Disease Research Center, in an interview with Healthline. Maybe 90 percent of the time the clinical diagnosis is accurate, a little bit less where there are atypical features.
In 2011, the National Institute on Aging developed a report with new guidelines for diagnosis. It incorporated a wealth of new research, including a number of tests that look at biomarkers in the body to diagnose Alzheimers disease.
For a rare few, a genetic test can reveal whether the person is likely to develop early-onset Alzheimers, a particularly swift-moving version of the disease.
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What Are The Challenges
While research on a cure is promising, there are some challenges. One is that we donât fully understand how HIV reservoirs work. Scientists are learning how to find, measure, and destroy them.
What about stem cell therapy? The CCR5 mutation that protects you from HIV is very rare, so itâs hard to find donor cells. Also, stem cell therapy is risky. People can reject donor cells and become very ill. Scientists are trying to find therapies that make a personâs own cells resistant to the virus, so they wonât need donor cells.
Another challenge is that males are the subjects of most HIV clinical trials, but about half of people with the virus are female. We need more studies to look at whether treatments will work on women and girls.
Even though research is very promising, it could be a few years before these treatments are tested to be sure they work well and are safe to use in many people who have HIV.
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Alzheimers Vaccine And Immunotherapy
Researchers have been attempting to develop a vaccine for Alzheimers disease for almost a decade. The strategy behind the immunotherapy approach is to use the bodys own immune system to destroy beta-amyloid plaques.
The first Alzheimers vaccine was tested in clinical trials in 2001. However, the trial was prematurely halted because six percent of participants developed serious brain inflammation. However, the vaccination did appear to benefit thinking and memory in some unaffected participants who were monitored after the end of the trial. Researchers have now developed a safer vaccine by using antibodies against a smaller fragment of the beta-amyloid protein, which they hope will avoid the complications of the previous trial.
Another approach to developing a vaccine involves using immunoglobulin, a filtered human blood product containing antibodies. Immunoglobulin was shown to be successful in a very small trial of 8 people with mild Alzheimers disease, with most showing improvement on tests of cognitive function after treatment. Although this trial is very small, it suggests the potential for larger trials of immunoglobulin therapy, which may have safety advantages over other vaccination techniques. Although this initial research is promising, much more research needs to be done before we know whether this approach will work.
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Diversifying The Drug Pipeline
Scientists all over the world are following a similar path. Theyre looking beyond the single strategy most dementia researchers have studied in the past clearing toxic amyloid plaques from the brain, a hallmark of Alzheimers disease and instead are pumping more possibilities than ever before into dementias drug pipeline.
The roles the immune system and the metabolic system play in the development of dementia are under the microscope. Researchers including many funded by the National Institutes of Health , which is expected to spend $2.8 billion on Alzheimers research in 2020 are also studying everything from blood vessels to hormonal factors to solve the dementia dilemma.
We now know that the brain is part of a larger system, explains Rebecca Edelmayer, director of scientific engagement at the Alzheimers Association. And there may be many other ways to target the overall health of the brain so that it stays as fit as possible throughout the aging process and is able to stave off signs and symptoms of Alzheimers disease and other dementias, she adds.
AARPs investment is one example of how we are working to improve the lives of older Americans. Millions of individuals and their families are affected by dementia, and the need for effective treatments has never been more critical.
Can Alzheimer’s Be Cured
P. Murali Doraiswamy discusses recent breakthroughs in diagnosing Alzheimer’s disease and what everyone can do to postpone the onset of memory loss.
Are you a scientist? Have you recently read a peer-reviewed paper that you want to write about? Then contact Mind Matters editor Jonah Lehrer, the science writer behind the blog The Frontal Cortex and the book Proust Was a Neuroscientist. His latest book isHow We Decide.
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A Clue To A Cure For Alzheimers Disease
- By Andrew E. Budson, MD, Contributor
Are you worried about Alzheimers disease? Does one of your parents or siblings have the disease? If so, your risks are between two and four times that of the general public. What about people without a family history of the disease? Unfortunately, everyone is at risk for it. By age 85, half of you reading this article today will have developed Alzheimers disease, with or without a family history.
Sounds pretty scary, doesnt it?
Im writing today to give you some good news. A new study from the lab of Harvard researcher Yakeel Quiroz, PhD, has suggested a new target for drugs that might have the potential to slow down or even stop Alzheimers disease in its tracks.
Q: If Drugs Against Amyloid Arent The Answer What Is
Back in the 80s and 90s, genetic tools weren’t quite developed enough to address the real question we had: What genes are involved in most cases of Alzheimers disease?
Techniques have advanced and we can now answer this question. New studiesmany led by Richard Mayeux, MD have been pointing to other processes in the brain. We also have better biological tools that can reveal the basic problem inside neurons.
Based on this research, the new consensus in the field is that there are two other pathways that cause the disease.
One involves protein trafficking, which is how proteins are shipped to different sites within a single cell. The health of neurons, more so than other cells, depends on protein trafficking in and out of one particular site: the endosome.
In Alzheimers, the flow of proteins out of the endosome is blocked, and we think that causes the other problems we see in the disease: the amyloid, the tau tangles also common in the Alzheimers brain, and the neurodegeneration. Essentially it’s a plumbing problem.
Our research here at Columbia provided some early evidence for an endosomal trafficking problem in Alzheimers. And genetic studiesincluding those led by Dr. Mayeuxhave now found that some endosomal genes are linked to Alzheimers, which provides more support.
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Promising Steps In The Right Direction
Currently available medications such as those which block the actions of an enzyme that destroys an important chemical messenger in the brain for memory or blocks the toxic effects of another messenger, glutamate temporarily manage symptoms. But new treatments are focused on slowing or reversing the disease process itself, by targeting the underlying biology.
One approach, called immunotherapy, involves creating antibodies that bind to abnormal developments in the brain , and mark them for destruction by a range of mechanisms. Immunotherapy is experiencing a surge of interest and a number of clinical trials targeting both amyloid- and tau are currently underway.
Aducanumab, an antibody targeting amyloid-, has shown promise in clinical trials and phase 3 trials are currently ongoing, as are several tau-based strategies. If any are successful, we would have a vaccine for Alzheimers.
Its estimated only 0.1% of antibodies circulating in the bloodstream enter the brain this also includes the therapeutic antibodies currently used in clinical trials. An approach my team is taking is to use ultrasound to temporarily open the blood-brain barrier, which increases the uptake of Alzheimers drugs or antibody fragments.
Lack Of Research Funding And Volunteers Hampers Progress
Although there has been good progress in the Alzheimers research field, organizations believe there is a lot more that needs to be done, particularly when it comes to funding.
James Pickett, head of research at the UKs Alzheimers Society, told us:
Dementia is the biggest health and social care challenge of our generation, but research into the condition has been hugely underfunded. This lack of funding has hampered progress and also restricted the number of scientists and clinicians working in the dementia field.
He is not wrong. In the US, for example, Alzheimers research received $504 million in funding from the National Institutes of Health last year, while cancer received more than $5 billion. Breast cancer alone even received more funding than Alzheimers, at $674 million.
Snyder told Medical News Today that this lack of funding is something that needs to be overcome in order to develop new treatment and prevention strategies for Alzheimers.
Other diseases have demonstrated that sustained investment in research can improve lives, reduce death rates and ultimately produce effective treatments and preventions, she said. We have the tools and the talent to achieve breakthroughs in Alzheimers disease, but we need the resources to make this a reality.
Dr. Ryan agrees, telling us:
In an attempt to tackle this problem, Snyder said the Alzheimers Association have launched a clinical trials matching service called TrialMatch.
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Stem Cells And Dementia
Stem cells are “building block” cells. They can develop into many different cell types, including brain or nerve cells.
Scientists have taken skin cells from people with certain types of dementia, such as Alzheimer’s disease, and “reprogrammed” them into stem cells in the lab. They’ve then triggered these stem cells to become brain cells.
These brain cells can also be used to test potential treatments at a very early stage.
We Need Your Help To Find A Cure Now
Dont let another minute pass. Help us before another victim cant care for themselves forgets their loved ones and loses years of their lives due to brain malfunction caused by dying Neuro-receptors.Our mission is to adequately fund highly credible institutions focused on researching Alzheimers disease and other forms of Dementia with the intent of finding a cure. Our exciting partnership with The University of Florida Health and McKnight Brain Institute, provides high hopes for not only attracting talented Neurologists looking to expand their training towards the world of research but also to fund those research fellows as they diligently search for a cure for Alzheimers disease and other forms of Dementia. The funds collected by the Alzheimers Research Foundation will also help pay for critical clinical trials and attract top researchers to one of the worlds most distinguished fellowship programs.
For more information on the signs of dementia, see this related article.
1 From the research report, Alzheimers Association, 2013 Alzheimers Disease Facts and Figures, Alzheimers & Dementia, Volume 9, Issue 2.
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