Researchers at the Biodemography of Aging Research Unit (BARU) at Duke University have recently published three interconnected studies that shed new light on how our genes, environment, and history of infections collide to influence the risk of Alzheimer’s disease (AD). By analyzing massive datasets from the UK Biobank, the Health and Retirement Study, and the Alzheimer’s Disease Neuroimaging Initiative (ADNI), this rigorous scientific work moves us closer to personalized prevention strategies for dementia.
The "Memory Center" and the NECTIN2 Gene
One study investigated the NECTIN2 gene, a known but often overlooked risk factor for Alzheimer's. The researchers found that a specific variation in this gene (the rs6859 ‘A’ allele) is directly linked to the shrinking, or atrophy, of the hippocampus—the brain’s primary hub for forming memories.
Interestingly, the NECTIN2 protein helps maintain the "glue" between cells and plays a role in how the brain defends itself against viruses. This suggests that people with this genetic variation might have a brain that is more vulnerable to infections, which in turn accelerates the loss of brain volume and increases the risk of Alzheimer's.
Can Vaccines Protect the Brain?
Building on the link between infections and brain health, BARU researchers explored whether repurposing common vaccines could help prevent Alzheimer's. Their findings were striking: people who received the shingles vaccine between the ages of 65 and 75 saw an overall 20% reduction in their risk of developing Alzheimer’s later in life.
The protection was even more dramatic for people with the NECTIN2 risk gene—especially women—where the vaccine was associated with significantly lower odds of the disease. This suggests that by preventing viral triggers like shingles, we may be able to shield genetically vulnerable brains from the "spark" that starts the neurodegenerative process.
The "Double Hit": Air Pollution and Infections
The third study highlights how our environment can make the effects of infections even worse. Researchers found that living in close proximity (less than 50 meters) to a major road—a proxy for high traffic-related air pollution (TRAP)—acts as a "second hit" to the brain.
While a history of infections alone increased the risk of dementia by 54%, individuals who dealt with both infections and high air pollution saw their risk jump by 164%. Curiously, this combined threat was most dangerous for people who do not carry the well-known APOE4 "Alzheimer’s gene". For those without the strong genetic risk of APOE4, avoiding environmental pollutants and staying up-to-date on vaccinations could be a powerful way to reduce the risk of dementia.
The Big Picture
Collectively, these studies from BARU demonstrate that Alzheimer’s is not determined by a single factor, but by a complex interplay of who we are (genetics), what we encounter (pollution), and how we protect ourselves (vaccines). This research paves the way for a future where doctors can offer tailored advice—such as prioritizing specific vaccines or environmental changes—based on an individual's unique genetic profile.
Citations
Vladimir A. Popov, Svetlana Ukraintseva, Hongzhe Duan, Arseniy Yashkin, Julia Kravchenko, Igor Akushevich, Heather Whitson, Konstantin G. Arbeev, and Anatoliy I. Yashin. "Traffic-related air pollution significantly aggravates the detrimental effect of infections on the risk of Alzheimer’s disease and other dementias, especially in non-carriers of APOE4." Frontiers in Dementia, 2026. https://doi.org/10.3389/frdem.2025.1668381
Hongzhe Duan, Svetlana Ukraintseva, Rachel Holmes, Deqing Wu, Arseniy P. Yashkin, Igor Akushevich, Anatoliy Yashin, and Konstantin Arbeev. "Towards personalized vaccine repurposing for Alzheimer’s prevention: Genotype-specific protective association of the shingles vaccine with odds of Alzheimer’s disease in participants of two large cohort studies." BMC Neurology, 2026. https://doi.org/10.1186/s12883-026-04728-5
Aravind Lathika Rajendrakumar, Konstantin G. Arbeev, Olivia Bagley, Anatoliy I. Yashin, and Svetlana Ukraintseva. "Lower hippocampal volume partly mediates the association between rs6859 in the NECTIN2 gene and Alzheimer’s disease: new findings from causal mediation analysis of ADNI data." Frontiers in Aging Neuroscience, 2026. https://doi.org/10.3389/fnagi.2026.1715773