Yale Study Links SARS-CoV-2 to Alzheimer's-Related Peptide Buildup

A recent study conducted by researchers at Yale University has uncovered a significant connection between SARS-CoV-2, the virus responsible for COVID-19, and the accumulation of amyloid beta peptides, which are associated with Alzheimer's disease. This groundbreaking research, published in the journal Science Advances on July 14, 2025, suggests that the neurological symptoms often reported by COVID-19 survivors, such as brain fog, may be linked to this peptide buildup in the retina.

The study aimed to explore the mechanisms behind the cognitive impairments observed in some individuals post-COVID-19. Senior author Dr. Brian Hafler, an associate professor of ophthalmology and visual science at Yale School of Medicine, noted that while the link between COVID-19 and brain fog has been documented, the exact biological processes remain elusive. "Our findings provide a potential biological explanation for the cognitive decline observed after COVID-19," Dr. Hafler stated.

Historically, Alzheimer's disease has been characterized by the accumulation of amyloid beta plaques in the brain, which are believed to disrupt neuronal function and contribute to cognitive decline. Researchers have speculated that amyloid beta may serve a protective role against pathogens, suggesting that its presence could indicate an immune response to viral infections. This hypothesis allowed researchers to investigate whether SARS-CoV-2 infection could similarly trigger amyloid beta accumulation.

Utilizing retinal organoids—miniaturized, simplified versions of the retina developed from human stem cells—the Yale team assessed the effects of SARS-CoV-2 on amyloid beta levels. Their findings confirmed that retinal cells from COVID-19 patients exhibited increased amyloid beta accumulation compared to those from healthy individuals, mirroring what is observed in Alzheimer's disease patients.

Dr. Hafler and his team utilized genetic engineering to create retinal organoids that mimicked the pathophysiological features of Alzheimer's disease, including genetic mutations that enhance amyloid beta production. They discovered that the SARS-CoV-2 spike protein could enter retinal cells through specific receptors, namely neuropilin-1 (NRP1) and angiotensin-converting enzyme 2 (ACE2). This viral entry resulted in heightened amyloid beta accumulation.

Remarkably, the team found that administering an NRP1 inhibitor could reverse amyloid beta buildup in retinal tissues treated with the SARS-CoV-2 spike protein. This discovery positions NRP1 as a potential therapeutic target for mitigating neurological complications following COVID-19 infection. However, Dr. Hafler cautioned that while the findings are promising, further clinical studies are needed to explore the long-term implications of SARS-CoV-2 infection on Alzheimer's disease risk.

The study's implications extend beyond immediate clinical applications; it bolsters the theory that microbial infections may exacerbate neurodegenerative conditions. Dr. Hafler emphasized the importance of understanding the potential relationships between viral infections and neurodegenerative diseases, stating, "This study opens new avenues for investigating how infections may contribute to the pathology of Alzheimer's disease."

Dr. Hafler's team plans to conduct further studies to evaluate whether early interventions could prevent the onset of Alzheimer's disease in individuals who have experienced COVID-19. Their ultimate goal is to develop strategies to reduce the long-term neurological effects of COVID-19 by targeting the pathways involved in amyloid beta aggregation.

As the medical community continues to grapple with the long-term effects of the COVID-19 pandemic, this study presents a critical step towards understanding the intersection of viral infections and neurodegenerative diseases. It highlights the need for ongoing research to unravel the complexities of brain health in the wake of COVID-19, potentially informing therapeutic strategies for both brain fog and Alzheimer's disease.