It can be difficult to conceptualize the total damage caused by Alzheimer’s. The neurodegenerative disease is a major cause of death in the US, killing more than 100,000 people annually. 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 burdens fall not only on patients but also on their loved ones, doctors and caregivers. Economically, the cost of caring for Alzheimer’s patients in 2020 is about $ 305 billion, according to a report by the Alzheimer’s Association. And that figure not includes 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. This is one of the reasons why hospitals and healthcare professionals are already strengthening the way they care for the elderly and Alzheimer’s patients. It takes 15 years to develop new treatments, and therefore adequate funding is needed for today’s research.
“Taking care of our older adults is a huge responsibility, one we are very proud of,” said Michael Dowling, President and CEO of Northwell Health. “Our aging population will be experiencing health issues, including and especially Alzheimer’s, which need the right care at the right time. That’s why we have expanded our services, including at Glen Cove Hospital, and research at the Feinstein Institutes for Medical Research.”
… the real suffering comes from the changes that happen in the personality …
What causes Alzheimer’s disease?
Although the cost of Alzheimer’s is clear, its causes remain frustratingly mysterious. Currently, there is no cure for the disease or treatments that stop its progression.
“Alzheimer’s is this brain problem and everyone knows what’s probably causing the problem, but no one could 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 likely drawn in contributors to the disease. The brains of Alzheimer’s patients reliably show two abnormalities: building up 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.
Yet it is unclear exactly how these proteins, or other factors such as inflammation, can cause Alzheimer’s disease.
“We are dealing with very complex components,” said Dr. Philippe Marambaud, a professor at the Feinstein Institutes and co-director of the Litwin-Zucker Alzheimer’s Research Center. “The real culprit is not clearly defined. We know there are three possible culprits [tau, beta-amyloid, inflammation]. They work in concert, or maybe in isolation. We do not know exactly. ‘
Many Alzheimer’s researchers have for years developed therapies that target beta-amyloid, which can accumulate 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. Eventually, the brain cells are destroyed.”
Unfortunately, clinical trials on 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, tau proteins lose their structure and form neurofibrillar tangles that block communication between synapses.
Credit: Adobe Stock
At the Feinstein Institutes, dr. Marambaud and his colleagues 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. It blocks synaptic communication. Dr. Marambaud said there are good reasons to think anti-tau therapies can treat Alzheimer’s effectively. ‘ [anti-tau therapies] can be more beneficial is that we have known for a very long time that 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, which are caused by mutations in the gene that encodes the tau protein. Thus, there is a direct genetic link between dementia and tau pathology. “To better understand how this protein interacts with Alzheimer’s, Dr. Marambaud and his colleagues have developed immunotherapies that focus on abnormal tau. Immunotherapies, such as vaccines, usually target infectious diseases… But it is also possible around the immune system of the body to prevent or treat some non-communicable diseases. Scientists have recently succeeded in treating certain types of cancer with immunotherapy, for example. “We have developed a series of monoclonal antibodies, which are basically the drugs that are needed. if you want to do immunotherapy, “said Dr. Marambaud.
Researchers at the Feinstein Institute are currently conducting promising clinical trials with anti-tau antibodies, some of which are in Phase III trials under the Food and Drug Administration. Patients receive these treatments intravenously within a few hours and will 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 and not cure it.
“Only the stabilization of the progression of the disease will save a great social, but also financial, burden,” said dr. Marambaud said. “As research progresses, we will improve these stabilization approaches to make them more effective.”
Even if anti-tau therapies are not the holy grail of Alzheimer’s treatments, they can alleviate severe behavioral symptoms of the disease and possibly 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 memory erosion. But the darkest consequences of the disease are often psychotic symptoms such as agitation, aggression and paranoia, according to Dr. Koppel, who not only examined Alzheimer’s but also treated Alzheimer’s patients for decades as a clinician. “My research focus comes from 20 years of sitting with Alzheimer’s families and listening to what is 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 take place in the personality and belief system that cause Alzheimer’s patients to ‘reject’ or even become violent towards their loved ones. At the Feinstein Institute, dr. Koppel’s research focuses on the relief of Alzheimer’s-related psychotic symptoms through anti-tau immunotherapies. “It’s our hypothesis that abnormal tau proteins in the brain somehow, downstream, affect the way people think,” Dr Koppel said. “And the impact it has is this paranoid, excited, psychotic phenotype.” Supporting this hypothesis is research on chronic traumatic encephalopathy (CTE), a degenerative disease involving the accumulation of abnormal tau. CTE, which is common among professional soccer players, also causes psychotic symptoms such as agitation, aggression and paranoia, and research shows that Alzheimer’s patients accumulate more abnormal tau in their brains, as measured by cerebrospinal fluid, that they show more psychotic symptoms and are more likely. to die earlier than patients with less abnormal tau. Given these strong links between psychosis and abnormal tau, Dr Koppel and his colleagues hope that anti-tau immunotherapies will alleviate psychosis in Alzheimer’s patients, who currently do not have safe and effective treatment options and are regularly given medication intended to treat psychosis. relieve people with schizophrenia. “We provide medication to Alzheimer’s patients that speeds up their cognitive decline and leads to bad outcomes, such as stroke and sudden death,” Dr Koppel said. “Nevertheless, schizophrenia medicine does treat some of the psychotic symptoms and aggressive behaviors associated with Alzheimer’s disease, and for many families it is crucial. We just do not have many options, and we urgently 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 is happening in the brain that makes people psychotic,” Dr Koppel said. “Once you have a biological treatment for psychosis that has an underlying pathophysiology, believe me, you can look at schizophrenia in new ways. Maybe it’s not going to be tough, 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. But this is currently impossible because scientists do not need the biomarkers and diagnostic tools to detect the disease before cognitive symptoms appear. It can take decades before prevention becomes 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 who have been identified to already be affected by dementia, with cognitive tests that can be done by the clinicians,” said Dr. Marambaud said. “And even better, maybe reduce the cognitive impairments.”
Dr Marambaud said he encouraged the public not to lose confidence.
“Be patient. It’s a very complicated disease,” he said. “Many laboratories are really committed to making a difference. Congress has also realized that this is a major priority. In the last five years, [National Institutes of Health] funding has increased tremendously. The scientific field is therefore working very hard. The politicians are behind the funding of 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, associated with Alzheimer’s,” the association wrote. “With few disadvantages and many known benefits, healthy lifestyle choices can improve your health and possibly protect your brain.”