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, but also causes worrying symptoms, such as agitation, paranoia and aggression.
These tasks fall not only to patients, but also to their loved ones, doctors and caregivers. Economically, the cost of caring for Alzheimer’s patients will reach about $ 305 billion in 2020, according to a report by the Alzheimer’s Association. And that figure not includes about $ 244 billion in unpaid care from family and friends.
The number of Alzheimer’s patients in the US is expected to double by 2050, affecting about 14 million people. This is why hospitals and health professionals are already working to strengthen 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 great responsibility that we are very proud of,” said Michael Dowling, president and CEO of Northwell Health. “Our aging population will face health problems, including Alzheimer’s, which will require proper care at the right time. That’s why we’ve expanded our services, including Glen Cove Hospital and research at the Feinstein Institute for Medical Research. “
… the real suffering comes from the changes that take place in the personality …
What causes Alzheimer’s disease?
While the costs of Alzheimer’s disease are clear, its exact causes remain frustratingly mysterious. Currently, there is no cure for the disease, nor any treatments to stop its progression.
“Alzheimer’s is this brain problem and everyone knows what is probably the cause of the problem, but no one has been able to do anything about it,” said Dr. Jeremy Koppel, geriatric psychiatrist and co-director of the Litwin-Zucker Alzheimer’s Research Center. .
But in recent decades, researchers have focused on the likely taxpayers of the disease. The brains of Alzheimer’s patients reliably have two abnormalities: the 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 are injured and die, and brain tissue shrinks.
However, it is not clear how these proteins or other factors, such as 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’s Research Center. “The real eggplant is not clearly defined. We know there are three possible culprits [tau, beta-amyloid, inflammation]. He works in concert or maybe in isolation. We don’t know exactly. “
Many Alzheimer’s researchers have spent years developing therapies targeting 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-cell communication and activate immune cells. These immune cells trigger inflammation. Eventually, the brain cells are destroyed.
Unfortunately, clinical trials of beta-amyloid therapies have not been effective in treating Alzheimer’s.
Anti-Tau Immunotherapies: The Holy Grail of Alzheimer’s?
In brains with Alzheimer’s disease, your proteins lose their structure and form neurofibrillation tangles that block communication between synapses.
Credit: Adobe Stock
At the Feinstein Institutes, Dr. Marambaud and colleagues focused on the less explored component of Alzheimer’s: abnormal tau. In healthy brains, your 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 your proteins. This blocks synaptic communication. Marambaud said there is good reason to believe 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 your pathology in the brain of the Alzheimer’s patient correlates much better with the progression of the disease and the loss of neuronal material in the brain “, compared to beta-amyloid, Dr. Marambaud said:” The second strong argument is that there are inherited dementias, called tauopathies, that are caused by mutations in the gene that encodes your protein. So there is a direct genetic link between dementia and your pathology. “To better understand how this protein interacts with Alzheimer’s, Dr. Marambaud and colleagues have developed immunotherapies that target your abnormal. Immunotherapies, such as vaccines, usually target infectious diseases. But it is also possible to use the body’s immune system to prevent or treat some non-infectious diseases. Scientists have recently managed to treat certain cancers with immunotherapies, for example. “We have developed a number of monoclonal antibodies, which are practically the therapy that is needed when you want to do immunotherapy,” said Dr. Marambaud.
Researchers at the Feinstein Institute are currently conducting promising ongoing clinical trials with anti-tau antibodies, some of which are in Phase III trials in the Food and Drug Administration. Patients receive these therapies intravenously over several hours and would 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 a huge societal and financial burden,” said Dr. Marambaud. As research progresses, we have improved these stabilization approaches to make them more effective.
Even if anti-tau therapies do not prove to be the holy grail of Alzheimer’s treatments, they could alleviate the severe behavioral symptoms of the disease and illuminate 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 memory erosion. But the darkest effects of the disease are often psychotic symptoms, such as agitation, aggression and paranoia, according to Dr. Koppel, who, in addition to Alzheimer’s research, has spent decades treating Alzheimer’s patients as a clinician. “My research comes from 20 years of living with Alzheimer’s families and listening to what’s the main issue,” said Dr. Koppel. “It’s never memory. It starts with memory as a diagnostic problem. But the real suffering comes from the changes that happen in the personality and belief system that make Alzheimer’s patients” ostracized or even become violent towards their loved ones. At the Feinstein Institute, Dr. Koppel’s research focuses on ameliorating Alzheimer’s-related psychotic symptoms through anti-tau immunotherapies. “Our hypothesis is that your abnormal proteins in the brain somehow, downstream, have an impact on the way people think,” Dr. Koppel said. “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 football players, also causes psychotic symptoms such as agitation, aggression and paranoia. having more chances to die faster than patients with your less abnormal. Given these strong connections between psychosis and abnormal tau, Dr. Koppel and colleagues hope that anti-tau immunotherapies will alleviate psychosis in Alzheimer’s patients, who currently lack safe and effective treatment options, and are often administers drugs to alleviate psychosis in people with schizophrenia. “We offer drugs to Alzheimer’s patients that accelerate cognitive decline and lead to poor outcomes, such as stroke and sudden death,” said Dr. Koppel. “However, schizophrenia drugs treat some of the psychotic symptoms and aggressive behavior associated with Alzheimer’s disease, and for many families this is crucial. We just don’t have many options and we desperately need more. ” Beyond treating Alzheimer’s patients, anti-tau immunotherapies can shed light on other mental illnesses. “Alzheimer’s can give us a window into what’s going on in the brain, which makes people psychotic,” Dr. Koppel said. “Once you have a biological treatment for psychosis that reaches a basic pathophysiology, believe me, you could look at schizophrenia in new ways. It may not be yours, but it may 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. But this is currently impossible, because scientists do not have the biomarkers and diagnostic tools needed to detect the disease before the onset of cognitive symptoms. It could take decades for prevention to become possible, if it ever happens.
In the short term, stabilizing Alzheimer’s 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 identified as already affected by dementia, with cognitive tests that can be done by doctors,” said Dr. Marambaud. “And even better, it can reduce cognitive impairments.”
Dr. Marambaud said he encourages the public not to lose faith.
“Be patient. It’s a very complicated disease,” he said. “A lot of labs are really committed to making a difference. Congress has also realized that this is a huge priority. In the last five years, [National Institutes of Health] funding has grown enormously. So the scientific field is working a lot. Politicians are behind us in funding this research. And it’s 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 reduce the risk of other diseases, such as heart disease and diabetes, which have been linked to Alzheimer’s,” the association wrote. “With a few known disadvantages and many benefits, healthy lifestyle choices can improve your health and possibly protect your brain.