Dr. Chhatwal discusses his research on Alzheimer’s disease and how funding from the American Brain Foundation played a pivotal role in his early career.
At the American Brain Foundation, we know that research is the key to discovering new treatments and cures for all brain diseases and disorders. This is why our Next Generation Research Grants are designed to promote innovative projects from early-career investigators that contribute to the future of brain disease research.
Jasmeer Chhatwal, MD, PhD, MMSc, Associate Professor of Neurology at Harvard Medical School, was the recipient of a Next Generation Research Grant from the American Brain Foundation in 2012. He now directs the Biomarkers of Neurodegeneration, Inflammation, and Cognitive Decline (BioNIC) laboratory at Massachusetts General Hospital, where researchers are working to develop blood tests that could enable earlier and more effective diagnosis of Alzheimer’s disease.
We spoke with Dr. Chhatwal about how his 2012 research grant influenced his career as a researcher and how his American Brain Foundation-funded project informed his later research on Alzheimer’s disease. He also discusses his hope for the future of Alzheimer’s treatment, how far research has come in the past 10 years, and why funding is so important for patients and clinicians everywhere.
Dr. Chhatwal’s responses below have been condensed and edited for clarity.
What inspired you to study the brain?
I started college as an architect—then I took a neurobiology course when I was a sophomore, and ever since, I’ve been a neuroscientist. I definitely have personal touchstones to brain disease, and I think that has helped me along the way. My grandfather died of a stroke. My grandmother had a condition called cerebral amyloid angiopathy, which is related to Alzheimer’s disease, and died of an intracranial hemorrhage. My other grandmother, unfortunately, has Alzheimer’s disease.
So there’s a lot in my family that brought me to the table, but I’m fascinated by it. It’s obvious that Alzheimer’s disease is hard to treat, but it’s so common and touches almost everyone’s life. There’s so much room for improvement in the way we treat it. To me, it’s always been very, very compelling, emotionally and intellectually.
What specific issue is your research trying to address?
For patients, the idea is to accelerate the development of treatments for Alzheimer’s disease. We have a few symptomatic therapies that are available, there are a few lifestyle changes we can suggest, but we lack drugs that are potent enough to change the course of the disease as of yet. That’s really beginning to change. There’s a lot of hope in the field that within the next year or two, we’re going to have some new drugs on the market, and that will lead the way to more and more effective treatments for Alzheimer’s disease.
People sometimes think the cognitive decline seen in Alzheimer’s disease is just a part of the aging process—perhaps an accelerated version of that—but what we’ve learned over the years is that they’re actually very different things. The normal aging process puts you at higher risk for cognitive decline, but it’s not inevitable that as people get older, they’re going to have cognitive decline.
My research is really intended to understand how to separate [cognitive changes due to] the normal aging process from Alzheimer’s disease and to provide tools and targets for future drug development.
How would better understanding biomarkers for Alzheimer’s enable us to improve treatment and diagnosis of the disease?
We need to identify people [at high risk for Alzheimer’s] early on, and we need to know what sort of things are absolutely central to the disease process that we can measure when we give medication. When we try to find a medication that changes the course of a disease, we need something called a biomarker. This allows us to know whether we’re using the drug at a proper dose, whether we’re engaging the target we want to engage, and over time, especially in a disease that evolves over years, whether or not we’re making progress.
What other factors do you consider when thinking about treatments for Alzheimer’s?
Another thing is that along with developing drugs, it’s important to have behavioral interventions that reduce the chances of developing Alzheimer’s disease in the first place. So we try to look at potentially modifiable risk factors. The ones that seem most prominent in terms of cognitive decline are things like elevated vascular risk factors, changes in sleep, and physical activity level. Those are the things we focus on the most, and all of them seem to have some sort of contribution to the likelihood that someone’s going to show cognitive decline.
Can the discovery of a certain treatment or cure for Alzheimer’s help with other diseases?
Yes. There are many different types of dementia, and many of them involve different types of protein buildups. If you develop techniques to identify specific proteins [responsible] for Alzheimer’s disease, some of those same techniques can also be applied to other diseases that involve protein buildups.
It’s also the case that as we treat Alzheimer’s disease, we also treat another condition called cerebral amyloid angiopathy, which frequently co-occurs with Alzheimer’s disease. It’s a very frequent cause of hemorrhagic stroke and can be a very serious disease in its own right. So that’s another way we can make a difference in other diseases.
Potentially modifiable risk factors like lack of exercise, smoking, and sleep disruption are really important for reducing the emergence of cognitive decline, but they’re also very important for reducing the risk of stroke and heart disease. So the idea is to develop technologies that have a broad reach in Alzheimer’s disease and also beyond—that can be used in clinical trial settings and to reduce risk factors for [conditions like] heart disease and stroke as well.
What do you hope your research will do to help patients? What do you want people living with Alzheimer’s to know?
Brain diseases are difficult to treat, but it’s not impossible. There are two phases [to research]: There’s understanding and there’s developing treatments. Both can advance at the same time, and I think that’s what we’re seeing right now. The better our understanding is, the more effectively we can target the disease.
I think Alzheimer’s disease is one of the most feared complications of aging. Individuals with Alzheimer’s disease lose a lot of the cognitive capacities they identify with their own personality and that allow them to meaningfully interact with their families. This also creates a huge burden for caregivers. Right now, there are over 16 million caregivers for Alzheimer’s disease patients in this country and over 5 million people that are affected. It’s one of the most pressing public health emergencies of our time.
But there’s good news on the horizon. There’s been a lot of progress in the last 10 years in Alzheimer’s disease research, and we’re starting to see that bear fruit in terms of new therapies and new approaches. For my patients, my hope is to give them more time with their families and their loved ones, and hopefully to reduce the caregiving burden on families as well.
How far has research come since you began your career? What kinds of exciting discoveries and developments have you seen since you entered the field?
The ability to diagnose Alzheimer’s disease has advanced tremendously with the development of amyloid PET scans, tau PET scans, and now blood-based biomarkers. It’s revolutionized the field. Even within the last two years, we’ve seen two drugs that have shown signs that they can actually slow down cognitive decline. That’s amazing! I think that’s the first time in human history where we’ve actually had the possibility of disease-modifying therapies for a common disease like Alzheimer’s disease.
This phase of Alzheimer’s disease therapeutics that we’re seeing now is targeting the amyloid protein. We’re going to start to see new therapies attacking the tau protein and reducing people’s risk overall by intervening in lifestyles and behaviors. My hope is that in a few years we’ll be able to do combination therapies, trying to treat the tau protein at the same time we’re reducing people’s risk of vascular disease.
So, it’s a very, very different field than it was 10 years ago. There’s a lot more hope and certainly a lot more understanding. We’re starting to see the fruits of [research] with new treatments that hopefully we’ll see very soon in clinics.
What did your American Brain Foundation-funded Clinical Research Training Fellowship enable you to work on?
The core objective of my fellowship was to try to identify changes in brain networks that distinguish early Alzheimer’s disease from normal age-related changes. That work created a foundation that allowed me to work with two groups.
One result of my fellowship has been my work with the Harvard Aging Brain Study, which is a long-running study that looks at older adults, some of whom are aging normally and some of whom have preclinical Alzheimer’s disease and eventually develop symptoms.
The second group is the Dominantly Inherited Alzheimer Network. Unfortunately, there are about 300 different genetic variants that can lead to Alzheimer’s disease at a very young age. There’s an international consortium to study these rare genetic variants. It’s rare for people to develop Alzheimer’s at a young age, so we don’t see age-related changes [in these individuals]. Looking at some of those contrasts allows us to focus on brain networks that distinguish aging from early Alzheimer’s disease. The idea is to develop a tool where we can identify people who are at risk.
What kinds of insights or discoveries did this research lead to?
The Harvard Aging Brain Study has been instrumental in developing new tools to look at cognitive decline and to develop PET scans and PET imaging as a core feature of clinical trials. I think that’s been one of its major impacts. Another thing it allowed us to do is really show the effect of elevated vascular risk factors together with even small amounts of amyloid buildup in the brain—that’s been one of my contributions in that study.
The Dominantly Inherited Alzheimer Network has been instrumental in identifying key core mechanisms of Alzheimer’s disease, identifying new drug targets, and looking at changes in the blood and cerebrospinal fluid that are indicative of early Alzheimer’s disease-related changes.
So both groups have been very influential, and I think our internationally known studies have made important contributions.
How did your early American Brain Foundation-supported research open doors for additional research funding or future research projects?
In several ways. [As an early-career researcher] you need dedicated time to develop your own ideas and to develop enough preliminary data that you can convince institutions like the National Institutes of Health (NIH) and other funding agencies to help your career development. The project the American Brain Foundation funded provided preliminary data for my career development award through the NIH.
Since the first day, the project has just grown exponentially, and now we’re fortunate to have three R1-level grants to support our work. The R1 is the central and most common award for independent research funding given out by the NIH. It’s sort of a benchmark grant for someone transitioning from being a supported investigator working with other people’s data to developing your own independent ideas and developing a research program of your own.
[The American Brain Foundation grant] was instrumental in terms of creating the time and helping me develop the ideas and the preliminary data that allowed us to do what we do today.
Why is funding research so important?
It’s important to fund research because there are diseases [like Alzheimer’s] that cause tremendous suffering. I think diseases like Alzheimer’s have been around for as long as humans have been around. When we see something that causes so much suffering, there’s a tendency to say, “The brain is too complex. We can’t treat it. We can’t change the course of this. This is part of aging.” But we’ve realized over time that we can intervene.
We’re starting to see the first interventions in human history against the buildup of the amyloid protein in the brain. But the way these things happen, the “behind-the-scenes” of research and technology development, all of that requires the concerted effort of large teams of scientists. It requires funding clinical trials that allow us to see whether or not particular treatments work, whether our understanding is correct, and whether the disease mechanisms we think are present are actually present. That’s how we find ways of altering the course of these very common and very burdensome human diseases—and the only way that gets done is if we put our effort, time, and money into it.
Why are organizations like the American Brain Foundation so important to supporting research?
I think the American Brain Foundation and the American Academy of Neurology are leading lights in terms of informing people about the importance of treating brain disease and that there’s hope to treat these very difficult-to-treat diseases. We need to encourage young, creative researchers to come into the field and apply their effort, time, and intellectual powers in new and innovative ways to problems that are really difficult to address.
So, in that respect, it’s not only [providing] hope, but actually enacting hope in order to understand and treat disease—engaging the people who can actually make that happen is the importance of the American Brain Foundation.
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