By Lillien Waller

Lauren Moo, M.D., ’84 and Marc Weisskopf, Ph.D., Sc.D.,’84 are two self-identified nerds who met at Commonwealth and went on to distinguished, and distinct, careers as scientists: Lauren as a cognitive behavioral neurologist and Marc as a neuroscientist and epidemiologist. Here they share what happens when the foundation you build on is not only shared research concerns, such as the human brain, aging, and dementia, but also a lifetime of friendship. 

The prevalence of neurodegenerative diseases in the United States—including Alzheimer’s disease and other dementias, and amyotrophic lateral sclerosis (ALS)—has been steadily rising for decades. ALS, also known as Lou Gehrig’s disease, affects some 30,000 people, and the life expectancy from the time of diagnosis is a mere two to five years. The impact of Alzheimer’s is even more staggering: as the seventh leading cause of death in the United States, it affects eleven percent of adults over the age of 65. That’s 7.2 million Americans.     

This is a tale of two studies conducted by Lauren Moo, M.D., and Marc Weisskopf, Ph.D., Sc.D.: the first focused on Alzheimer’s; the other, on ALS. Regarding the earlier research, Lauren and Marc point out that our understanding of Alzheimer’s has changed dramatically in the last twenty years. The scientific community no longer assumes that people are cognitively healthy until they develop dementia later in life, Lauren says. It is, in all likelihood, tied to an earlier set of life circumstances—health conditions like long-term hypertension, yes, but also environmental exposures. They asked: what if we could trace the onset of neurodegenerative diseases like Alzheimer’s to environmental factors that occurred during a window of exposure decades earlier?

How It Started

Lauren and Marc both recall that theirs was a small class, and their friend group comprised close-knit kids who, as Lauren says, “were all math and science-y. Marc and I did our homework together on the phone, but our extracurriculars were different. He was doing baseball and theater, and I was always doing dance.” Marc interjects with an update about a mutual friend; Lauren notes that until recent years, their careers have taken them to different regions of the country or the world. They crosstalk and edit each other’s recollections the way lifetime friends tend to do.     

After Commonwealth, Lauren attended Cornell University, graduating with a degree in chemistry. Marc graduated from Brown University, studying neuroscience. She went on to medical school and a residency in neurology, and he studied for his doctorate in neuroscience and a Doctor of Science in epidemiology. They remained in touch over the years, visiting periodically and running into each other at professional conferences.     

A cognitive behavioral neurologist, Lauren’s current research focuses on dementia caregivers and how the use of telehealth and other technologies might support them and the older veterans they serve. Marc’s epidemiological research examines the influence of environmental risk factors on such health outcomes as autism spectrum disorders, ALS, cognitive function and dementia, and psychiatric conditions. When they began working together nearly fifteen years ago, their individual research interests didn’t overlap (and still mostly don’t).     

“Our research was not at all amenable to collaboration,” Lauren recalls, “before I moved from working full time at Mass General—at which point I had been doing a lot of functional MRI and cognitive neuroscience research—to working most of the time as a researcher at the VA [Bedford Veterans Affairs Medical Center]. But being a researcher at the VA opened the door for me to do more with big datasets and clinical-trials research.” It was then that Marc noticed that this new direction in Lauren’s research, which included her connection to the Bedford VA’s Alzheimer’s patient ward, might offer an opportunity for the two to work together, because, as Lauren notes, the Bedford VA has the largest in-patient dementia unit population of any VA in the country.     

“Her work aligned perfectly with something I was trying to do with Alzheimer’s disease,” Marc explains. “Then we realized that maybe we could do a study within the VA system that could benefit from her access to a large number of Alzheimer’s patients. The research involved teeth, too, and there was a dental clinic there. I had come across this idea of using teeth much earlier, because your teeth are a little fossil record of what was going on when you were in utero, if it’s a baby tooth, or, if it’s an adult tooth, in the very early years of life.”     

Marc and Lauren received an NIH grant to conduct the research, but the study was fraught with a number of logistical challenges, not least of which was how to obtain the teeth. If an Alzheimer’s patient came into the dental clinic and needed a tooth extracted for other reasons, they would need to have a system in place for obtaining it. Similarly, once someone had passed away, they would need to coordinate with the staff performing the autopsy procedure in order to obtain a tooth. The study was complicated and unwieldy on a number of levels. But this initial Alzheimer’s study, while not exactly successful, inspired related research—including a current study by Marc that relies on information extracted from tens of thousands of baby teeth, the owners of which are now in their late sixties. It also, albeit indirectly, led to Lauren and Marc’s current ALS research.

How It’s Going

Twenty years ago, Marc led a study that was the first to identify the connection between military service broadly (rather than just Gulf War service that had previously been noted) and the onset of ALS later in life. Other researchers have since found the same thing, Marc says, but no one has conclusively determined why.     

Their current project uses extensive VA data to look at why military service is correlated with an increased risk of ALS. “This is a different study that is not fraught with the kinds of challenges that we had with the Alzheimer’s study,” Lauren explains. “We’re not trying to recruit people. We’re not reliant on dentists or medical examiners to perform autopsies. We don’t need to coordinate with funeral homes or enroll individual participants. This ALS study is what we call a big data study; it looks at existing data across the whole VA, which is the largest single healthcare network in the country.      

“Some of this is all about timing. The Alzheimer’s study was in response to a particular call for proposals from the NIH about environmental exposures and the risk factors for Alzheimer’s. This new study took advantage of the fact that for the first time, there is an attempt to integrate information in the VA database with the Department of Defense (DOD) database, which for whatever reason had never been linked. They weren’t previously ‘talking to each other.’ That happened a year or so before we submitted our ALS proposal to the CDC. I told Marc that this was a new opportunity for us to connect the dots between military service and patients’ current health outcomes.” A few days before the two spoke with CM, they had just submitted their first paper on the research for publication. But if we now generally accept that dementia and cognitive decline begin earlier in life, how are Lauren’s and Marc’s research any different?      

First, Lauren notes, most current modeling of these diseases don’t begin the timeline for environmental exposure as far back as Marc has done in his research—that is, as far back as the womb. But, more significantly, they also believe that “cognitive reserve” holds the key. “We now know that it’s not just something that happens to you in your fifties or sixties,” Lauren says. “The degree to which you will actually manifest symptoms that we would categorize as either mild cognitive impairment or dementia is mitigated by how intellectually resilient you are.”     

Marc illustrates the point by citing the Nun Study, a famous longitudinal study begun in 1986 that, among other results, found that those who had achieved a bachelor’s degree or higher and those who wrote with more linguistic complexity when young were less likely to develop Alzheimer’s disease later in life.     

“We know, for example, that there is a significant percentage of people who are autopsied after they pass away who don’t clinically have dementia but who do have Alzheimer’s pathology,” Lauren says. “When they have looked at those people, there is a greater percentage who have higher academic or occupational achievement. That’s where this idea of cognitive reserve comes in,” Lauren says, referring to the so-called buffer of intellectual ability. “Some people can weather the storm better.”

Lauren Moo, M.D., is Associate Professor of Neurology at Harvard Medical School, staff of the Neurology Department at Massachusetts General Hospital, and Site Director of the Bedford Division of the New England Geriatric Research Education and Clinical Center, U.S. Dept. of Veterans Affairs. Marc Weisskopf, Ph.D., Sc.D., is the Cecil K. and Philip Drinker Professor of Environmental Epidemiology and Physiology at the Harvard T.H. Chan School of Public Health in the departments of Environmental Health and Epidemiology, Director of the Harvard T.H. Chan NIEHS Center for Environmental Health, and Director of Epidemiological Studies for the Football Players Health Study at Harvard. Lillien Waller is a poet, essayist, and editor. Her essays focus primarily on the intersection of art and personal history. In 2023, she was awarded an Arts Writers Grant from The Andy Warhol Foundation for the Visual Arts to profile interdisciplinary artists of color in her hometown, Detroit.