Alzheimer’s disease is an unforgiving illness. It robs people of their memories and their identities, taking a brutal toll on individuals, families and society. The most common form of dementia, Alzheimer’s disease affects an estimated six million Americans—a number that is expected to reach 14 million by 2060.
The disease is a complex puzzle, but one that is beginning to take shape. Among the experts helping put the pieces together are renowned researchers and physicians at the Mount Sinai Health System and the Icahn School of Medicine at Mount Sinai. They shared their thoughts about the most promising treatments for Alzheimer’s disease, now and on the horizon.
Georges Naasan, MD
Associate Professor of Neurology
Medical Director, Division of Behavioral Neurology and Neuropsychiatry
Co-Medical Director, the Barbara and Maurice Deane Center for Wellness and Cognitive Health
Since I began caring for patients with Alzheimer’s disease, we haven’t had many medications to offer. The only medications we’ve had were drugs developed in the 1990s. They work by giving healthy brain cells a boost of the chemical messenger acetylcholine. They make it seem as if cognitive decline slows down, but the disease is still moving along inside the brain.
Now, the U.S. Food and Drug Administration has approved some new drugs, Leqembi® (lecanemab) in July 2023 and Aduhelm® (aducanumab) in 2021.
Some doctors have questioned whether the side effects of aducanumab outweigh its benefits, but so far, lecanemab is showing more promise. Both are in a class of drugs known as amyloid immunotherapies, which can help clear amyloid plaques in the brain. In people with mild cognitive impairment or early symptoms of dementia, amyloid immunotherapies appear to slow down but not stop the disease. While that is encouraging, we still don’t have scientific evidence that confirms amyloid plaques are the underlying cause of Alzheimer’s disease. There are many other changes in the brain that occur with Alzheimer’s that these drugs do not target.
While I’m cautious about what amyloid immunotherapies can achieve, it is still exciting to have something to offer patients. Of course, our treatment for patients is multipronged. At the Barbara and Maurice Deane Center for Wellness and Cognitive Health, our team includes physicians, psychiatrists, social workers, nurses, nurse practitioners and other specialists, all working together to help patients living with dementia and their families. That includes things like treating mental health issues like anxiety and depression, working with families to develop safe living situations, brainstorming about finances, helping with caregiver support and so many other services.
In the future, I think drugs targeting amyloid will be combined with those that target other brain changes in Alzheimer’s disease. We still need scientists to continue working to understand the causes of the disease. What starts that ticking time bomb that eventually leads to memory loss and other symptoms? I’m so grateful to be at Mount Sinai, where I’m surrounded by such a dedicated team of providers and where we can work closely with so many talented researchers. We’re continuously thinking about how to incorporate new discoveries so that we can serve our patients better.
Fanny Elahi, MD, PhD
Assistant Professor of Neurology, Neuroscience and Pathology, Molecular and Cell-Based Medicine
Director of Fluid Biomarker Research, the Barbara and Maurice Deane Center for Wellness and Cognitive Health
Co-Director of Genetics and Genomics Core, Alzheimer’s Disease Research Center
I believe the reason it has taken so long to find impactful treatments for Alzheimer’s disease is that it isn’t just one disease. There are many different pathways to the same end problem in the brain. We need to understand those different pathways to treat them more precisely. And we can begin to do that now that we have tools available to measure the molecular signatures of Alzheimer’s disease in the blood.
My lab focuses on developing new methods to measure those molecular signatures, or biomarkers. Right now, we treat Alzheimer’s disease when someone has symptoms. But by that point, a lot has gone wrong in the brain. With blood biomarkers, we can detect disease before people have symptoms. And we can develop highly precise treatments that target different underlying disease processes. I am hopeful that some of those treatments will come quickly, by repurposing drugs that have already been approved for other disorders. I think in the not-so-distant future, we will have blood tests for brain health. But there will have to be a shift in the culture. We have been treating Alzheimer’s disease like a box: you are either in it or you’re not. It’s a continuum. If we treat it like a continuum, we will be able to make use of blood markers to put people into a risk category, much as we do with blood tests that measure cholesterol levels.
When you go to your primary care doctor, they don’t put you in a box based on your cholesterol level. Instead, they put you into a risk category and intervene to prevent heart disease based on that category. Blood biomarkers will also allow us to estimate a person’s risk of Alzheimer’s disease, so we can intervene with lifestyle modifications and treatments before they have irreversible symptoms. We are starting to shift the perception of Alzheimer’s from a deadly, incurable disease to one we can do something about. I imagine that in a few years, we will be treating each Alzheimer’s patient differently, depending on what drives their disease. These blood biomarkers are taking our interventions to the next level.
Alison M. Goate, DPhil
Jean C. and James W. Crystal Professor of Genomics
Chair of Genetics and Genomic Sciences
Founding Director, Ronald M. Loeb Center for Alzheimer’s Disease at Mount Sinai
My lab uses genetic approaches to understand Alzheimer’s disease. What has been frustrating is that for decades, promising findings from animal research just haven’t translated to treatments for humans. But now, two new drugs—Leqembi® (lecanemab) and Aduhelm® (aducanumab)—have been approved for Alzheimer’s disease, and another similar drug, called donanemab, is likely to be approved within the next few months. These drugs are based on hypotheses that came out of human genetic research published three decades ago. It has been a long time coming.
These new treatments are a type of drug known as amyloid immunotherapies. They are designed to clear amyloid fragments from the brain. The treatments have only modest effects on cognition. However, they help to confirm the hypothesis that beta-amyloid is central to the disease process. It’s an important first step and I think there will be second-generation drugs to follow that will be even more effective.
There are other promising treatments on the horizon. Over the last 10 or 15 years, my lab has focused on trying to understand the genetic components of sporadic late-onset Alzheimer’s disease. We discovered that much of the genetic risk is related to immune cells in the brain called microglia, which clear debris. If you think of amyloid as the garbage, these cells are like garbage collectors. That finding is leading drug companies to new kinds of therapeutics—treatments designed to amp up those “garbage collectors.”
Meanwhile, researchers are learning more about the apolipoprotein E (APOE) gene, which is the strongest genetic risk factor for late-onset Alzheimer’s disease. In addition to the common APOE4 variant, which increases risk, several other APOE variants have now been identified that appear to protect against the disease. If we can understand how they work, we may be able to mimic their effects in people who don’t have the protective versions of the gene.
I believe we need to develop multiple drugs that target many different mechanisms and combine them for maximum effect. At the Ronald M. Loeb Center for Alzheimer’s Disease at Mount Sinai, we have many researchers looking at the disease from different angles. I’m optimistic because we’ve identified so many new targets. I think that in the next decade, the way we think about and treat Alzheimer’s disease is going to change dramatically.
