Both COVID-19 and Alzheimer’s Disease have had devastating and disproportionate effects on African Americans. Three Rutgers University researchers seek to address important gaps in understanding not only the cognitive, neural, and immunological consequences of COVID-19 in older African Americans but also how those consequences can impact this population’s risk for Alzheimer’s Disease.

With a recently awarded, one-year grant for $643,396 from the National Institutes of Health’s National Institute on Aging (NIA), Mark A. Gluck, PhD, Patricia Fitzgerald-Bocarsly, PhD, and Maria Laura Gennaro, MD, are collaborating to explore the links between COVID-19 and Alzheimer’s disease, asking questions including:  

  • What differentiates older COVID-19 “long haulers” from those who recovered from COVID-19 fully?
  • Why is age a risk factor for both COVID-19 and Alzheimer’s disease?
  • Does having had COVID-19 increase one’s future risk for Alzheimer’s disease?
  • Is one’s future risk for Alzheimer’s disease-related to the severity of COVID-19 symptoms?

“We have a longer-term goal to use these questions about COVID-19 as a starting point for addressing broader aims about how does immunological health, and anything that impacts immunological health, affect aging and Alzheimer's disease,” says Gluck, the Principal Investigator on the new award and a cognitive neuroscientist and professor of neuroscience and public health at Rutgers University-Newark.

Gluck’s broader research program focuses on the cognitive, computational, and neural bases of learning and memory, the consequences of memory loss due to aging, post-traumatic stress disorder (PTSD), and Alzheimer’s disease, as well as how sleep and exercise can improve cognition and brain health. The new collaborative award on COVID-19 and brain health is a supplement to Gluck’s ongoing NIA grant on Risk Factors for Future Cognitive Decline and Alzheimer's Disease in Older African Americans.

It is Gluck’s role as director of the Aging & Brain Health Alliance at Rutgers University-Newark that uniquely qualifies him to foster interdisciplinary research and community-based collaboration to understand aging, brain health, and Alzheimer’s disease.

African Americans have been so severely affected by both Alzheimer’s disease and COVID-19, it is especially important that they be included as research participants in research designed to understand specifically why, and how, both diseases have affected this community.

Mark A. Gluck, PhD

Professor of Neuroscience and Public Health, School of Arts and Sciences-Newark; Director of Aging & Brain Health Alliance, Rutgers-Newark

With 15 years of partnerships with churches and community organizations in New Jersey, and enrolling nearly 450 older African Americans over the last five years into research studies as part of his Pathways to Healthy Aging in African Americans, Gluck has the expertise and experience to close crucial knowledge gaps about COVID-19 and its relationship to Alzheimer’s disease, especially among African Americans.

This new award will also allow Gluck and his co-Investigators to expand their Pathways to Healthy Aging in African Americans cohort of African Americans aged 60 years and above to continue to study them for years to come.

“This is an observational study,” Gluck says. Referring to the enrolled research participants, he adds, “We want to understand who they are, how they are, how their brain, their cognition, and their immune system is. And we want to understand the relationships between all of those now, and the relationships between how they are now and what happens to them in a year, or two years, or four years.”

Among the research participants to be enrolled in the new study, Gluck estimates that about 40% will not have been infected with the SARS-CoV-2 virus that causes COVID-19, and the other 60% will be COVID-19 survivors of three types: (1) those who suffered a severe case of COVID-19 and required hospitalization; (2) those who experienced mild or moderate COVID-19 symptoms but were able to receive treatment at home; and (3) those who were asymptomatic carriers and tested positive for the coronavirus antibodies.

Gluck says for the protection of his lab’s staff and those participating in the study, all research participants enrolled in the study will need to first be fully vaccinated.

“For additional safety in this pandemic era, we also ask all participants go to the Clinical Research Unit at the Rutgers New Jersey Medical School (NJMS), where they are administered a COVID infection test two days before they begin our studies. This allows the researchers to exclude (or at least delay testing) anyone who is currently positive for SARS-CoV-2 infection.”

For asymptomatic carriers, how will the researchers distinguish who has had the SARS-CoV-2 virus, especially after they have been vaccinated?

“One of the challenges is that standard antibody tests only assess whether or not there is an immune response to the corona – the crown-like spikes on the coronavirus’ surface,” says Gluck. “Once somebody is vaccinated, a standard antibody test will not tell you anything because everyone who has been vaccinated will respond, because the vaccine-based immune response is specific to the crown that’s on the virus spikes. “Rather,” Gluck adds, “You need specialized tests that look for immunity response to the other parts of the virus, including the nucleus. That is why Dr. Maria Gennaro is a key part of our team.”

Maria Laura Gennaro, MD, is a professor of medicine at NJMS, a Principal Investigator at the medical school’s Public Health Research Institute, and a professor of epidemiology and biostatistics at the Rutgers School of Public Health. At the beginning of the COVID-19 pandemic, Gennaro established a Spike-protein-based test to detect anti-SARS-CoV-2 antibodies. For this NIA-funded research study, the Gennaro Lab plans to address questions on the relationship between antibody response, and clinical manifestation of COVID-19.

Marila Gennaro RGHI
Maria Laura Gennaro, MD, Professor of Medicine, New Jersey Medical School
Photo courtesy of Rutgers Global Health Institute

Gennaro’s expertise and research will be key to distinguish between antibodies developed only in response to vaccination and antibodies generated in response to prior SARS-CoV-2 infection. The types of antibodies that COVID-19 vaccines aim to teach our bodies to make in order to protect against infection are the antibodies that attach themselves to the spikes that surround the coronavirus’s outer shell.

Gluck says, “Dr. Gennaro looks for SARS-CoV-2 specific responses to the nucleus of the virus. The idea is that this specific response to the nucleus of the virus will only be present in someone who has actually had COVID-19, regardless of whether or not they have been vaccinated.” Currently, COVID-19 vaccines do not generate an antibody response against the nucleus of the SARS-CoV-2 coronavirus.

It is not yet fully understood why age is a risk factor for both COVID-19 and Alzheimer’s disease, but understanding the mechanism that leads to immune dysfunction may be crucial for the development of effective treatment, and that’s where Fitzgerald-Bocarsly comes in.

“Normally, one function of the immune system is to help clear out senescent cells that accumulate in the body as we age, causing damage to a variety of organ systems,” says Fitzgerald-Bocarsly, one of the new award’s co-investigators and provost of Rutgers Biomedical and Health Sciences–Newark.

Fitzgerald-Bocarsly’s research focuses on the human innate immune response to viral infections within the context of aging. She is a professor and the vice-chair for research of the department of pathology and laboratory medicine at NJMS.

Better understanding of these connections is expected to lead to clinical approaches that target detrimental immune senescence and increase not only the lifespan of individuals but also the healthspan...

Patricia Fitzgerald-Bocarsly, PhD

Professor of Pathology and Laboratory Medicine, New Jersey Medical School; Provost, Rutgers Biomedical and Health Sciences-Newark

A recent study by Fitzgerald-Bocarsly suggested that older individuals have an increasing buildup of CD8+ (cytotoxic) T cells that are senescent, meaning they are no longer fully functional; these cells serve as a critical component of the adaptive immune response system. CD8+ T cells are white blood cells that, when functional, can directly kill virus-infected cells, but in older individuals, these white blood cells become senescent – or cease to divide or support the tissues of which they are a part – due to DNA damage.

“We hypothesize that the immune system, including T-cells, becomes dysregulated through the accumulation of senescent cells, contributes to inflammaging (chronic low-grade inflammation that develops with advanced age) and to many diseases associated with aging like dementia, autoimmunity, cardiovascular disease, and the detrimental effects of infectious diseases like influenza virus and SARS-CoV-2,” says Fitzgerald-Bocarsly.

Cellular stress, like the immune response to infections, can trigger T-cell senescence. When senescent T-cells are not efficiently cleared out of the body, the ability of immune system to ward off viral infection may be affected and this may explain why older adults are, in general, less able to fight off and survive SARS-CoV-2 infection. SARS-CoV-2 infection may lead to long-lasting CD8+ T cell dysfunction and increased levels of CD8+ T-cell senescence.

Fitzgerald-Bocarsly adds, “Better understanding of these connections is expected to lead to clinical approaches that target detrimental immune senescence and increase not only the lifespan of individuals but also the healthspan – that is, the number of years during which an aging individual enjoys good health and mental acuity.”

This NIH-funded study – and the collaboration between Gluck, Fitzgerald-Bocarsly, and Gennaro – seeks to close the gap on the cross-sectional relationship between immune health and cognitive/brain health, specific interrelationships between COVID-19 history and severity, T-cell senescence, capacity for SARS-CoV-2 antibody and T-cell memory responses, and cognitive/brain health. If COVID-19 history and T-cell senescence are shown to relate to brain health, it may indicate whether these immune health variables predict future cognitive decline.

With so many unknowns, why study the links between COVID-19 and Alzheimer’s disease in African Americans?

Dr. Gluck speaking into a microphone to a room of mostly seated adults
Dr. Mark Gluck and Glenda Wright (both standing) offer brain health education at the Newark Housing Authority's Clubhouse in Newark, NJ (April 2019)

Gluck shares a memorable anecdote, “Glenda Wright, one of the members of our community outreach team who oversees all our relationships with public housing, introduced something in one of her presentations. Glenda asked a room of older African American seniors, ‘How many of you have pills in your medicine cabinet that you take regularly?’ Well, in this audience at that age range, basically everybody’s hands were raised. And Glenda continued, ‘All of you with your hands raised… the only reason those pills are saving your life today is that someone in past years participated in the research. It’s now your opportunity to pay it forward.’”

Gluck adds, “So when people ask us what the benefit of participating is, we say, what you’re doing is paying it forward to help eradicate Alzheimer’s disease for future generations. Because African Americans have been so severely affected by both Alzheimer’s disease and COVID-19, it is especially important that they be included as research participants in research designed to understand specifically why, and how, both diseases have affected this community.”