Gene Reduces Benefit of Exercise in Preventing Alzheimer’s

Summary: Carrying the risk variant of the ABCA7 gene reduces the ability of exercise to increase cognitive performance and memory abilities in older African Americans, increasing the risk for Alzheimer’s disease.

Source: Rutgers University

In the first study of its kind, neuroscience researchers at Rutgers University–Newark’s Center for Molecular and Behavioral Neuroscience (CMBN) have found that an important genetic variation associated with Alzheimer’s disease regulates the ability of physical fitness to help ward off the condition in African Americans, who are twice as likely to suffer from the disease as white Americans. The results of this Externalnew study, funded by a five-year grant to Professor Mark A. Gluck from the National Institute of Health’s National Institute on Aging (NIA), was recently published in the journal Frontiers in Aging Neuroscience.

Gluck, a neuroscientist who has been studying Alzheimer’s disease and other memory disorders for decades, led the study along with his postdoctoral fellow, Neha Sinha, and research assistant, Chelsie Berg. Gluck is Director of the ExternalAging & Brain Health Alliance at Rutgers University-Newark, which fosters interdisciplinary and university-community collaboration to expand our understanding of aging, brain health, and the prevention of Alzheimer’s disease, especially in populations with elevated risk for dementia, such as African Americans.

Scientists have long known that modifiable behaviors such as diet, exercise and physical fitness reduce the risk, or delay the onset, of Alzheimer’s disease and other forms of dementia. According to Gluck, what is new about these findings is that “the presence of a risk variant of the ABCA7 gene appears to diminish the ability of physical fitness to increase cognition and memory abilities in older African Americans, thereby indirectly increasing their risk for Alzheimer’s disease. This may be an important contributing factor to the disparities in rates of Alzheimer’s disease among African Americans.”

For their recent study, Gluck and his team studied 100 healthy African Americans from Newark, age 55 to 86, with an average age of 67. The group included 20 men and 80 women, some carrying the non-risk gene variant, while others carried the higher-risk variant. In addition to completing several tests of cognition, including tasks that measure learning and memory ability, all participants were given a thorough assessment of their physical fitness, especially their cardiovascular, or aerobic, endurance.

For carriers of the non-risk genotype, higher levels of physical fitness were significantly associated with fewer cognitive errors, while there was no noticeable relationship between physical fitness and cognition for those carrying the risk genotype.

It has long been known that being physically fit and exercising regularly can reduce the risk of cognitive decline and Alzheimer’s disease. Moreover, increased levels of aerobic activity have also been shown to increase the physical size of the hippocampus, a key brain region for learning and memory which is the site of some of the earliest signs of Alzheimer’s disease in the brain. What is new and exciting about these recent findings from the Rutgers-Newark team is that they have shown, for the first time, that the link between physical fitness and improved cognition can be modulated by a genetic risk factor for Alzheimer’s disease in African Americans.

For Gluck and his team, the implications of these findings are significant for several reasons. “First, they provide us with a novel insight into one reason why African Americans may be at higher risk for Alzheimer’s disease as compared to white Americans,” says Gluck. “As such, these finding could lead to a deeper understanding of the unique pathways to Alzheimer’s disease that put African Americans at higher risk and thus point us towards new approaches to therapeutic or behavioral changes that could reduce the burden of Alzheimer’s on African Americans. Second, these findings provide us with a better understanding of the mechanisms by which physical fitness can improve and strengthen the brain. Because so few African Americans have participated in aging and Alzheimer’s research in the past, we know far too little about race-specific risk factors for Alzheimer’s disease. Recruiting more African Americans to participate in this research is necessary if we are going to advance the science of aging to benefit everyone.”

This is a blue DNA double helix
For carriers of the non-risk genotype, higher levels of physical fitness were significantly associated with fewer cognitive errors, while there was no noticeable relationship between physical fitness and cognition for those carrying the risk genotype. The image is in the public domain.

An important limitation of the current study, as Gluck notes, is that “these results are based on a comparison, at a single point in time, between different people of varying levels of physical fitness. What remains to be established is whether or not variations in the ABCA7 gene can affect the degree to which adhering to a regular program of physical exercise can improve cognition in an individual over the long term.” To answer that question, Gluck and colleagues, with financial support from the New Jersey Department of Health, have partnered with local churches, senior centers, and federally-subsidized housing sites to study how cardio-fitness dance classes can improve cognition and brain function in older African Americans. The results of this ongoing study may help identify what behavioral and lifestyle interventions can reduce the high burden of Alzheimer’s disease.

About this neuroscience research article

Rutgers University
Media Contacts:
Mark A. Gluck – Rutgers University
Image Source:
The image is in the public domain.

Original Research: Open access
“ABCA7 Risk Genotype Diminishes the Neuroprotective Value of Aerobic Fitness in Healthy Older African Americans”. Chelsie N. Berg, Neha Sinha and Mark A. Gluck.
Frontiers in Aging Neuroscience. doi:10.3389/fnagi.2019.00073


ABCA7 Risk Genotype Diminishes the Neuroprotective Value of Aerobic Fitness in Healthy Older African Americans

Although the association of ABCA7 risk variants with Alzheimer’s disease (AD) has been established worldwide, its effect size on the relative odds of being diagnosed with AD is significantly higher in African Americans. Across ethnicities, two common ABCA7 loci (rs115550680 and rs3764650) have been confirmed to increase the risk of AD. While ABCA7 rs115550680 has been linked to the development of late-onset AD in African Americans, no association between ABCA7 variant rs3764650 and AD has been found in this population. In order to elucidate the influence of ABCA7 rs3764650 on AD risk in African Americans, we sought to investigate the relationship between this variant, aerobic fitness, and cognition. The present study tested the hypothesis that in African Americans, ABCA7 rs3764650 confers an indirect risk for AD via its interaction with aerobic fitness, a modifiable lifestyle factor known to attenuate AD-related neuropathology. In a case-control sample of 100 healthy African Americans, we observed that ABCA7 rs3764650 genotype modulates the association between aerobic fitness and a cognitive assessment of generalization following rule learning. For carriers of the non-risk genotype, higher levels of aerobic fitness were significantly associated with fewer generalization errors, while carriers of the risk genotype did not show any relationship between aerobic fitness and generalization. Our findings imply that ABCA7 rs3764650 risk genotype may diminish the neuroprotective effects of aerobic fitness, and, they suggest differing risk patterns between cognitive decline and fitness by ABCA7 genotype. Thus, in African Americans the interactive effects of ABCA7 rs3764650 and aerobic fitness likely compound overall ABCA7-related AD risk, and may contribute to health disparities whereby African Americans are at a higher risk for dementia, with double the prevalence of AD.

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