It can be difficult to imagine the total damage caused by Alzheimer’s. Neurodegenerative disease is a leading cause of death in the US, killing more than 100,000 people every year. And as Alzheimer’s progresses in the brain, it not only affects memory but also causes troubling symptoms such as agitation, paranoia and aggression.
These burdens fall not only on patients, but also on their loved ones, doctors and caregivers. Economically, the cost of caring for Alzheimer’s patients was an estimated $ 305 billion in 2020, according to a report from the Alzheimer’s Association. And that figure not comprise an estimated $ 244 billion in unpaid care provided by family and friends.
The number of Alzheimer’s patients in the US is expected to double by 2050, affecting approximately 14 million people. That is one reason why hospitals and health professionals are already working to strengthen care for the elderly and Alzheimer’s patients. It takes 15 years to develop new treatments, so today’s research needs adequate funding.
“Caring for our older adults is a big responsibility, a responsibility of which we are very proud,” said Michael Dowling, president and CEO of Northwell Health. “Our aging population will face health challenges, including and especially Alzheimer’s disease, that require the right care at the right time. That’s why we expanded our services, including at Glen Cove Hospital, and research at the Feinstein Institutes. for Medical Research. “
… the real suffering comes from the changes taking place in the personality …
What Causes Alzheimer’s?
While the costs of Alzheimer’s disease are clear, the exact causes remain frustratingly mysterious. Currently, there is no cure for the disease, nor treatments to stop its progression.
“Alzheimer’s is this brain problem, and everyone actually knows what’s likely causing the problem, but no one has been able to do anything about it,” said Dr. Jeremy Koppel, a geriatric psychiatrist and co-director of the Litwin-Zucker Alzheimer’s Research Center. .
But in recent decades, researchers have focused on potential contributors to the disease. The brains of Alzheimer’s patients reliably display two abnormalities: accumulations of proteins called abnormal tau and beta-amyloid. As these proteins build up in the brain, they disrupt healthy communication between neurons. Over time, neurons are injured and die, and brain tissue shrinks.
Still, it’s unclear how these proteins, or other factors, such as inflammation, can cause Alzheimer’s disease.
“We are dealing with very complicated components,” said Dr. Philippe Marambaud, a professor at the Feinstein Institutes and co-director of the Litwin-Zucker Alzheimer Research Center. “The actual culprit is not clearly defined. We know that there are three possible culprits [tau, beta-amyloid, inflammation]. They work together, or maybe alone. We don’t know exactly. ‘
Many Alzheimer’s researchers have spent years developing therapies that target beta-amyloid, which can build up to form plaques in the brain. The Alzheimer’s Association writes:
“According to the amyloid hypothesis, these stages of beta-amyloid aggregation disrupt cell-to-cell communication and activate immune cells. These immune cells cause inflammation. Ultimately, brain cells are destroyed.”
Unfortunately, clinical trials of beta-amyloid therapies have not been effective in the treatment of Alzheimer’s disease.
Anti-Tau Immunotherapies: The Holy Grail of Alzheimer’s?
In brains with Alzheimer’s disease, tau proteins lose their structure and form neurofibrillary tangles that block communication between synapses.
Credit: Adobe Stock
At the Feinstein Institutes, Dr. Marambaud and colleagues focused on the less researched Alzheimer’s component: abnormal tau. In healthy brains, tau plays several important functions, including stabilizing internal microtubules in neurons. But in the brains of Alzheimer’s patients, a process called phosphorylation changes the structure of tau proteins. This blocks synaptic communication. Marambaud said there are good reasons to think anti-tau therapies can effectively treat Alzheimer’s disease. “The main argument about why [anti-tau therapies] more beneficial is that we have known for a long time that tau pathology in the brain of the Alzheimer’s patient correlates much better with disease progression and loss of neuronal material in the brain “compared to beta-amyloid, Dr. Marambaud said:” The second strong argument is that there are hereditary dementias called tauopathies that are caused by mutations in the gene encoding the tau protein. So there is a direct genetic link between dementia and tau pathology. ”To better understand how this protein interacts with Alzheimer’s disease, Dr. Marambaud and colleagues have developed immunotherapies that target abnormal tau. Immunotherapies, such as vaccines, usually target infectious diseases. But it is also possible to use the body’s immune system to prevent or treat certain non-contagious diseases. Scientists have recently succeeded in treating certain cancers with, for example, immunotherapies. “We’ve developed a series of monoclonal antibodies, which are basically the therapies you need to do immunotherapy,” said Dr. Marambaud.
Researchers at Feinstein Institutes are currently conducting promising ongoing clinical trials with anti-tau antibodies, some of which are in phase III trials under the Food and Drug Administration. Patients receive these therapies intravenously over several hours and would undergo multiple rounds of treatment. It’s comparable to chemotherapy.
In the short term, anti-tau therapies are more likely to help stabilize, not cure, Alzheimer’s disease.
“Just stabilizing the progression of the disease will save a huge social as well as financial burden,” said Dr. Marambaud. “As the research progresses, we would improve these stabilization approaches to make them more and more effective.”
Even if anti-tau therapies don’t prove to be the holy grail of Alzheimer’s treatments, they can potentially alleviate serious behavioral symptoms of the disease and potentially alleviate some of the mechanisms behind psychosis.
Alzheimer’s and Psychosis
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When most people think of Alzheimer’s, they tend to focus on the erosion of memory. But the darkest effects of the disease are often psychotic symptoms such as agitation, aggression and paranoia, said Dr. Koppel, who, in addition to researching Alzheimer’s disease, treated Alzheimer’s patients as a physician for decades. “My research focus comes from 20 years of sitting with Alzheimer’s families and listening to what the main problem is,” said Dr. Couple. It is never memory. It starts with memory as a diagnostic problem. But the real suffering comes from the changes that are taking place in the personality and belief system that make Alzheimer’s patients “rejected or even violent towards their loved ones. Institutes, Dr. Koppel’s research focuses on alleviating Alzheimer’s-related psychotic symptoms through anti-tau immunotherapy. ”It is our hypothesis that abnormal tau proteins in the brain are somehow downstream. , affect the way people think, “said Dr. Koppel.” And the impact it has is this paranoid, agitated, psychotic phenotype. “This hypothesis is supported by research on chronic traumatic encephalopathy (CTE), a degenerative disease in which abnormal tau builds up. CTE, common in professional football players, also causes psychotic symptoms such as agitation, aggression and paranoia. In addition, research shows that the more abnormal tau accumulated in their brains, as measured by cerebrospinal fluid, the more psychotic and more likely to die earlier than patients with less abnormal tau, given these strong links between psych ose and abnormal tau, Dr. Koppel and colleagues believe that anti-tau immunotherapies will relieve psychosis in Alzheimer’s patients, who currently lack safe and effective treatment options and are often given medications designed to relieve psychosis in people with schizophrenia. “We give Alzheimer’s patients drugs that accelerate their cognitive decline and lead to poor outcomes such as stroke and sudden death,” said Dr. Couple. “Nonetheless, the schizophrenia drugs treat some of the psychotic symptoms and aggressive behaviors associated with Alzheimer’s, and for many families this is crucial. We just don’t have many options, and we urgently need more.” In addition to treating Alzheimer’s patients, anti-tau immunotherapies can shed light on other mental health conditions. “Alzheimer’s can give us a glimpse into what goes on in the brain that makes people psychotic,” said Dr. Couple. “Once you have a biological treatment for psychosis that comes to an underlying pathophysiology, believe me, you could look at schizophrenia in new ways. Maybe it won’t be tau, but it could be a paradigm for treating mental illness. “
The future of Alzheimer’s treatments
Dr. Marambaud said the long-term goal of anti-tau immunotherapies is to prevent Alzheimer’s disease. But that’s currently impossible because scientists lack the biomarkers and diagnostic tools needed to detect the disease before cognitive symptoms appear. It could take decades for prevention to become possible, if ever.
In the short term, stabilizing Alzheimer’s disease is a more realistic goal.
“Our hope is that the treatments will be aggressive enough so that we can at least stabilize the disease in patients who have been identified as already suffering from dementia, with cognitive testing that can be performed by the clinicians,” said Dr. Marambaud. “And even better, maybe the cognitive impairment will lessen.”
Dr. Marambaud said he encourages the public not to lose faith.
“Be patient. It’s a very complicated disease,” he said. “Many labs are really committed to making a difference. Congress has also recognized that this is a huge priority. Over the past five years [National Institutes of Health] funding has increased dramatically. So the scientific field is working very hard. The politicians are behind us in funding this research. And it is a complicated disease. But we will make a difference in the years to come. “
Meanwhile, the Alzheimer’s Association notes that physical activity and a healthy diet can reduce the chances of developing Alzheimer’s, although more large-scale studies are needed to better understand how these factors interact with the disease.
“Many of these lifestyle changes have been shown to lower the risk of other diseases, such as heart disease and diabetes, that are associated with Alzheimer’s,” the association wrote. “With few drawbacks and many known benefits, healthy lifestyle choices can improve your health and potentially protect your brain.”