As the pandemic rages on across the globe, scientists have started identifying a chilling pattern: An estimated one-third of people infected with COVID-19 develop neurological symptoms including strokes, headaches, and disturbed consciousness. In some brains, COVID causes molecular changes that mirror those seen in the brains of people with Alzheimer’s, leading some scientists to believe that long COVID may be an atypical form of the memory-destroying disorder. There are also larger concerns that damage to the brain caused by COVID may put individuals at an increased risk of developing dementia later in life. The downstream effects on long-term health are far from understood, but dramatic preliminary evidence suggests a complicated alignment with Alzheimer’s disease.
Amid an overall push to better understand long COVID—on April 5, President Joe Biden ordered a new research initiative across federal agencies—there is also a worldwide effort to study this insidious link to Alzheimer’s, with various groups racing to understand the overlap between COVID and neurological harm. In New Jersey, one project stands out for incorporating another critical overlapping factor: the people at high risk of developing both severe COVID and Alzheimer’s.
Rutgers University researchers are currently enrolling older Black adults in an observational study examining the consequences of COVID and how these relate to risk for Alzheimer’s. The neurodegenerative disease disproportionately affects Black Americans, with the CDC anticipating case counts increasing over the next 40 years. COVID is also deadlier for Black Americans, a reality stemming from long-standing public health inequities.
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Although there are some obvious risk factors that exacerbate the effects of COVID and Alzheimer’s on Black populations (such as increased rates of diabetes stemming from poor nutrition), scientists still do not fully understand why these health disparity gaps are so large, Mark Gluck, a professor of neuroscience and public health at Rutgers University-Newark, told The Daily Beast. Genetics and differences in immune systems may play a role, but specific ideas are hard to come by yet.
Gluck spearheads the ongoing COVID-Alzheimer’s study, alongside Patricia Fitzgerald-Bocarsly, an immune system researcher and Provost of Rutgers Biomedical and Health Science-Newar, and Maria Laura Gennaro, a professor of medicine and epidemiology at Rutgers. By examining the questions surrounding COVID—like why age is a risk factor and why some develop long-haul symptoms—the team hopes to “gain insights into Alzheimer’s disease that we would never have had otherwise,” said Gluck.
In some ways, examining what COVID has to do with the brain is really a proxy for understanding the immune system’s effect on the brain. It’s known that the immune system plays a role in the development of Alzheimer’s: People with the disease have faulty microglia (a type of immune cell), and chronic inflammation is generally thought to drive cognitive decline. It’s possible, Gluck explained, that “to some degree, Alzheimer’s may be like an autoimmune disorder,” in which immune cells attack healthy brain cells and damage brain tissue via inflammation.
COVID can induce an immune response in the brain, which may explain why some people develop brain fog and memory loss. This may mirror what is happening in the brains of people with Alzheimer's. “It also suggests that Alzheimer’s researchers, who mostly talk to scientists studying neurodegenerative diseases, should be talking more to immunologists,” Gluck said.
Fitzgerald-Boscarly is one of those immunologists. While scientists have been interested in the intersection of the immune system and neuroscience for decades, she told The Daily Beast that what’s happening now is a maturation of the field boosted by advanced research tools. Early in her career, she was in the lab that saw some of the very first patients with HIV in New York. HIV also triggers inflammation, which can damage the brain.
“In a sense, my career to date has been bookended by these two pandemics: HIV and COVID,” Fitzgerald-Boscarly said.
In June 2020, Fitzgerald-Boscarly released findings that in older adults, there’s a buildup of cytotoxic T cells (which kill cancerous or infected cells) that no longer function due to aging—what biologists call senescent cells. She believes that an accumulation of these faulty cells in older people may, in part, drive up chronic low-grade inflammation that contributes to diseases like dementia. Their presence may also explain why COVID is deadlier for older people.
The team is especially curious about the gene variants APOE4 and APOE2—which are known to play a role in Alzheimer’s risk. APOE4 is the strongest risk factor gene for Alzheimer’s disease, and early research suggests it also increases the risk of developing severe COVID. Meanwhile, APOE2 appears to protect against developing Alzheimer’s disease. The question now is whether or not it may also shield asymptomatic patients from the most serious outcomes of COVID.
Supported by a grant from the National Institutes of Health awarded in April 2021, the Rutgers study is currently enrolling Black adults over 60 in the Newark area. The goal is to build a cohort of 200 to 300 participants, half of whom have had varying degrees of COVID and half who have not. They will be asked about their sleep, fitness, cognitive status, and overall health while participating in genotyping and brain scans.
Dr. Alexander Salerno is a partner in this recruitment. He runs Salerno Medical Associates, a family-owned practice that serves the communities of Newark and East Orange, New Jersey. His practice serves roughly 20,000 residents across five clinics, including 6,000 older Black individuals—at least half of whom came down with COVID between 2020 and 2021.
When Salerno looks back on when COVID first hit his community, it’s with pride and astonishment. As other practices closed, his clinics stayed open. In spring 2020, the Salerno Medical Associates partnered with Rutgers to get FDA approval for saliva testing and subsequently went to work, testing hundreds of patients a day. The rules were constantly changing and resources were nearly impossible to get.
“It was really tough in the beginning,” Salerno told The Daily Beast. “Our offices are technically in federally underserved areas when it comes to primary care. Now add a pandemic to that. Our urban community was very vulnerable.”
Today, Salerno sees “many different degrees of long haul syndrome.” But it’s difficult to know what is strictly COVID-caused or not. Many of his patients paused care during the worst of the pandemic, and in turn, many cases of diabetes, hypertension, and cardiovascular disease got worse. He suspects some patients who had COVID but don’t show signs of further illness yet may still in the future. “The summation of it all we have yet to truly understand,” Salerno says.
When Salerno gauges patient interest in participating in the Rutgers study, it’s within an overall conversation about brain health. His goal is to destigmatize dementia and educate his patients on the controllable factors, like diet and exercise, that can modify risk and severity.
Gluck believes the community-oriented nature of Salerno’s practice, along with its history, motivates its clients to participate in the study. Salerno’s parents founded the practice in the 1950s, and after the 1967 Newark riots erupted amid racial tensions, they stayed while other businesses left. The practice also serves patients through three programs designed to expand access to care and increase healthcare knowledge
“We feel this is important because healthcare is not a one-size-fits-all approach,” Salerno said. “Not everyone can get to a clinic or doctor’s office, and when they do, there’s a lot of disservice as opposed to good service.”
In the far future, that service may include care for Alzheimer’s informed by participation in the Rutgers study.
“From the diagnosis point of view, understanding the role of the immune system in Alzheimer’s could help us understand who’s most at-risk,” Gluck says.
Furthermore, knowing which aspects of the immune system are exactly involved could lead to therapeutic interventions that target them. This necessitates much more research, Fitzgerald-Boscarly explains. For example, it’s known that drugs called senolytics clear senescent cells. But because evolution has allowed senescent cells to accumulate, it’s possible there’s some benefits. The trick will be determining how to make quality therapies, without inadvertently causing harm.
For now, the focus of the research is to study people at increased risk for Alzheimer’s and COVID and look for patterns, but there are plans to collaborate with other universities and examine the immune system reactions of older adults who were hospitalized with COVID. They are “pressing into this area of neuroimmunology,” Fitzgerald-Boscarly said. “As a scientist, no two days are the same—as studies grow and evolve, there’s the joy of discovery.”
