It can be difficult to conceptualize the total damage caused by Alzheimer’s. Neurodegenerative disease is one of the leading causes of death in the United States, causing the deaths of 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 burdens fall not only on patients, but also on their loved ones, doctors, and caregivers. Economically, the cost of caring for Alzheimer’s patients reached an estimated $ 305 billion by 2020, according to a report by the Alzheimer’s Association. And that figure it doesn’t includes an estimate of $ 244 billion in unpaid care provided by family and friends.
The number of Alzheimer’s patients in the United States is projected to double by 2050 and affect about 14 million people. This is one of the reasons 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 current research needs adequate funding.
“Caring for our older adults is a big responsibility, of which we are very proud,” said Michael Dowling, president and CEO of Northwell Health. “Our aging population will face health problems, including Alzheimer’s, that will require proper care at the right time. That’s why we’ve increased our services, including Glen Cove Hospital, and research. at the Feinstein Institute for 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 unclear, its exact causes remain frustratingly mysterious. Currently, there is no cure for the disease, nor treatments that stop its progression.
“Alzheimer’s is this brain problem and everyone knows what’s 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 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 show two abnormalities: the accumulation 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.
However, it is not clear exactly how these proteins, or other factors such as inflammation, can lead to Alzheimer’s.
“We are facing 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 culprit is not clearly defined. We know there are three possible culprits [tau, beta-amyloid, inflammation]. They work in concert or perhaps in isolation. We don’t know for sure. “
Many Alzheimer’s researchers have been developing beta-amyloid-targeted therapies for years, which can build up forming 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 trigger inflammation. Ultimately, the cells brain cells are destroyed. “
Unfortunately, clinical trials of beta-amyloid-targeted 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 neurofibrillary tangles. messes that block communication between synapses.
Credit: Adobe Stock
At the Feinstein Institutes, Dr. Marambaud and colleagues have focused on the least explored component of Alzheimer’s: abnormal tau. In healthy brains, tau has several important functions, including stabilizing the internal microtubules of 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 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 tau 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, The second strong argument is that there are inherited dementias, called tauopathies, that are caused by mutations in the gene encoding the tau protein. Therefore, there is a direct genetic link between dementia and tau pathology. “To better understand. as this protein interacts with Alzheimer’s, Dr. Marambaud and colleagues have developed abnormal tau-targeted immunotherapies. Immunotherapies, such as vaccines, often 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 forms of cancer with immunotherapies, for example. “We have developed a number of monoclonal antibodies, which are basically the therapy required when you want to do immunotherapy,” Dr. Marambaud said.
Researchers at the Feinstein Institute 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 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 and not cure it.
“Simply stabilizing the progression of the disease will save a huge social burden, but also a financial one,” Dr. Marambaud said. “As research progresses, we will improve 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 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 darker effects of the disease are often psychotic symptoms such as agitation, aggression and paranoia, according to Dr. Koppel, who, in addition to researching Alzheimer’s, spent decades treating Alzheimer’s patients as a clinician. “My research focus comes from 20 years of sitting with Alzheimer’s families and hearing what the main problem is,” said Dr. Koppel. “It’s never memory. It starts with memory as a diagnostic problem. But the real suffering comes from the changes that occur in the personality and belief system that make Alzheimer’s patients” ostracized or even violent. towards their loved ones. At the Feinstein Institutes, Dr. Koppel focuses on relieving 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. “And the impact it has is this paranoid, agitated psychotic phenotype.” This hypothesis supports research on chronic traumatic encephalopathy (CTE), a degenerative disease involving the accumulation of abnormal tau. CTE, common among professional football 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 the brain, measured through the cerebrospinal fluid, they present more psychotic symptoms and are Considering these strong connections between psychosis and abnormal tau, Dr. . Koppel and colleagues hope anti-tau immunotherapies will alleviate psychosis in Alzheimer’s patients, who currently have no safe and effective treatment options. They are often given medications designed to relieve psychosis in people with schizophrenia. “We are giving drugs to Alzheimer’s patients that accelerate their cognitive impairment and lead to poor outcomes, such as stroke and sudden death,” said Dr. Koppel. “However, medications 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.” Beyond the treatment of Alzheimer’s patients, anti-tau immunotherapies can illuminate other mental illnesses. “Alzheimer’s can give us a window into what’s going on in the brain that makes people psychotic,” Dr. Koppel. “Once you have a biological treatment for psychosis that achieves an underlying pathophysiology, believe me, you could look at schizophrenia in new ways. It may not be tau, 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 cognitive symptoms appear. It could be decades before prevention is possible, if at all.
In the short term, stabilizing Alzheimer’s is a more realistic goal.
“Our hope is that the treatments will be aggressive enough at least to be able to stabilize the disease in identified patients who are already affected by dementia, with cognitive tests that doctors can do,” Dr. Marambaud said. “And even better, maybe reduce cognitive impairment.”
Dr. Marambaud said he encourages the public not to lose faith.
“Have patience. It’s a very complicated disease,” he said. “Many labs are really committed to the difference. Congress has also realized that this is a high priority. In the last five years, [National Institutes of Health] funding has increased enormously. Therefore, the scientific field is working very hard. Politicians are behind us in funding this research. And it is a complicated disease. But we will make a difference in the coming years. “
Meanwhile, the Alzheimer’s Association notes that physical activity and a healthy diet can reduce the chances of developing Alzheimer’s, although 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,” he wrote. association. “With few known drawbacks and many benefits, healthy lifestyle choices can improve your health and possibly protect your brain.”