It can be difficult to conceptualize the total damage caused by Alzheimer’s. Neurodegenerative disease is the leading cause of death in the United States, killing more than 100,000 people each year. And as Alzheimer’s progresses in the brain, it not only erodes memory, it also causes worrying symptoms like agitation, paranoia and aggression.
These burdens fall not only on patients, but also on loved ones, doctors and caregivers. Economically, the cost of caring for Alzheimer’s patients reached about $ 305 billion in 2020, according to a report by the Alzheimer’s Association. And that figure no include about $ 244 billion in unpaid care provided by family and friends.
The number of Alzheimer’s patients in the United States is expected to double by 2050, affecting about 14 million people. This is one of the reasons why hospitals and health professionals are already working to reinforce the way they 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, which we are very proud of,” said Michael Dowling, president and CEO of Northwell Health. “Our aging population will face health problems, including and especially Alzheimer’s, which will require the right care at the right time. That is why we have increased our services, including Glen Cove Hospital and research at the Feinstein Institutes of Medical Research.”
… the real suffering comes from the changes that happen in the personality …
What causes Alzheimer’s disease?
While the costs of Alzheimer’s are clear, its exact causes remain frustratingly mysterious. Currently, there is no cure for the disease, nor treatments to prevent its progression.
“Alzheimer’s is the brain problem, and everyone kind of knows what is probably 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 Litwin-Zucker Alzheimer Research Center.
But in recent decades, researchers have focused on likely contributors to the disease. The brains of Alzheimer’s patients reliably show two abnormalities: accumulation of proteins called abnormal tau and beta-amyloid. As these proteins accumulate in the brain, they disrupt healthy communication between neurons. Over time, neurons get hurt and die, and brain tissue shrinks.
Still, it is unclear exactly how these proteins, or other factors like inflammation, can cause Alzheimer’s.
“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 real culprit is not clearly defined. We know that there are three possible culprits [tau, beta-amyloid, inflammation]. They are working together or perhaps in isolation. We don’t know exactly. “
Many Alzheimer’s researchers have spent years developing therapies that target beta-amyloid, which can accumulate to form plaque in the brain. The Alzheimer’s Association writes:
“According to the amyloid hypothesis, these stages of beta-amyloid aggregation interrupt cell-to-cell communication and activate immune cells. These immune cells trigger inflammation. Ultimately, brain cells are destroyed.”
Unfortunately, clinical trials of therapies that target beta-amyloid have not been effective in treating Alzheimer’s.
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 his colleagues have focused on the least explored component of Alzheimer’s: abnormal tau. In healthy brains, tau performs several important functions, including stabilizing internal microtubules in neurons. But in the brain 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 that anti-tau therapies can effectively treat Alzheimer’s. “The main argument around why [anti-tau therapies] could be more beneficial is that we have known for a long time that the tau pathology in the brain of the Alzheimer’s patient correlates much better with the progression of the disease and with the 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, which are caused by mutations in the gene that codes for the tau protein. Therefore, there is a direct genetic link between dementia and the pathology of tau. “To better understand how this protein interacts with Alzheimer’s, Dr. Marambaud and his colleagues have developed immunotherapies that target abnormal tau. Immunotherapies, like vaccines, usually target infectious diseases. But it is also possible to use the immune system of the body to prevent or treat some non-infectious diseases. Scientists have recently been able to treat certain forms of cancer with immunotherapies, for example. “We have developed a series of monoclonal antibodies, which are basically the necessary therapy when you want to have immunotherapy,” said Dr. Marambaud .
Currently, researchers at the Feinstein Institutes are conducting promising clinical tests with anti-tau antibodies, some of which are in phase III testing by the Food and Drug Administration. Patients receive these therapies intravenously for several hours and undergo several rounds of treatment. It is similar to chemotherapy.
In the short term, anti-tau therapies are more likely to help stabilize Alzheimer’s, not cure it.
“Only stabilizing the progression of the disease will save an enormous social, but also financial, burden,” said Dr. Marambaud. “As the research progresses, we would improve these stabilization approaches to make them increasingly effective.”
Even though anti-tau therapies do not prove to be the Holy Grail of Alzheimer’s treatments, they could potentially alleviate the severe behavioral symptoms of the disease and potentially illuminate some of the mechanisms behind psychosis.
Alzheimer’s and psychosis
Credit: Getty Images
When most people think about Alzheimer’s, they tend to focus on memory erosion. But the darkest effects of the disease are often psychotic symptoms like agitation, aggression and paranoia, according to Dr. Koppel, who, in addition to researching Alzheimer’s, has spent decades treating Alzheimer’s patients as a clinician. “My research focus comes from 20 years of sitting with Alzheimer’s families and listening to what the main problem is,” said Dr. Koppel. “It is never memory. It starts with memory as a diagnostic problem. But the real suffering comes from the changes that happen in the personality and the belief system that make Alzheimer’s patients” ostracized or even violent towards their loved ones. At the Feinstein Institutes, Dr. Koppel’s research focuses on relieving psychotic symptoms related to Alzheimer’s through anti-tau immunotherapies. “It is our hypothesis that abnormal tau proteins in the brain in some way, downstream, affect the way people think,” said Koppel. “And the impact it has is this paranoid, agitated, psychotic phenotype.” Supporting this hypothesis is research on chronic traumatic encephalopathy (CTE), a degenerative disease that involves the accumulation of abnormal tau. CTE, common among professional soccer players, also causes psychotic symptoms such as agitation, aggression and paranoia. In addition, research shows that as Alzheimer’s patients accumulate more abnormal tau in their brains, as measured by cerebrospinal fluid, they exhibit more psychotic symptoms and are more likely to die earlier than patients with less abnormal tau. Given these strong connections between psychosis and abnormal tau, Dr. Koppel and his colleagues hope that anti-tau immunotherapies will relieve psychosis in Alzheimer’s patients, who currently lack safe and effective treatment options and generally receive medications designed to relieve psychosis in people with schizophrenia. “We are administering medications to Alzheimer’s patients that accelerate their cognitive decline and lead to poor results, such as stroke and sudden death,” said Koppel. “However, drugs for schizophrenia treat some of the psychotic symptoms and aggressive behavior related to Alzheimer’s disease, and for many families, this is crucial. We just don’t have many options and desperately need more.” In addition to treating Alzheimer’s patients, anti-tau immunotherapies can shed light on other mental illnesses. “Alzheimer’s can give us a window into what happens in the brain that makes people psychotic,” said Koppel. “After having a biological treatment for psychosis that comes to an underlying pathophysiology, believe me, you could look at schizophrenia in new ways. Maybe it’s not tau, but it can be a paradigm for treating mental illness.”
The future of Alzheimer’s treatments
Dr. Marambaud said that the long-term goal of anti-tau immunotherapies is to prevent Alzheimer’s. But this is currently impossible because scientists lack the biomarkers and diagnostic tools needed to detect the disease before cognitive symptoms appear. It may take decades before prevention becomes possible, if ever.
In the short term, stabilizing Alzheimer’s is a more realistic goal.
“Our hope is that the treatments will be aggressive enough that we can at least stabilize the disease in patients identified as already affected by dementia, with cognitive tests that can be done by doctors,” said Dr. Marambaud. “And even better, it may reduce cognitive impairments.”
Dr. Marambaud said that he encourages the public not to lose faith.
“Be patient. It is a very complicated disease,” he said. “Many labs are really committed to making a difference. Congress has also realized that this is a high priority. In the past five years, [National Institutes of Health] funding has increased tremendously. Therefore, the scientific field is working hard. Politicians are with us to fund 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 further large-scale studies are needed to better understand how these factors interact with the disease.
“Many of these lifestyle changes decrease the risk of other diseases, such as heart disease and diabetes, which have been linked to Alzheimer’s,” wrote the association. “With few known disadvantages and many benefits, healthy lifestyle choices can improve your health and possibly protect your brain.”