COVID-19 and Its Potential Role in Alzheimer’s Disease Through Retinal Amyloid Accumulation

A recent study conducted by Yale researchers has shed light on the possible connection between SARS-CoV-2 infection and Alzheimer’s disease, specifically focusing on how the virus may trigger the buildup of Alzheimer's-related peptides in the retina. This groundbreaking research provides new insights into the neurological symptoms associated with COVID-19, such as brain fog, and explores the potential mechanisms behind these effects.

The hallmark of Alzheimer’s disease is the formation of amyloid beta plaques in the brain, which are linked to cognitive decline. Interestingly, amyloid beta peptides are believed to serve a protective role against microbial infections, functioning as part of the brain’s innate immune response. However, in Alzheimer’s patients, these peptides can accumulate excessively, potentially due to a compromised blood-brain barrier that allows pathogens to invade.

In their study published in Science Advances, Yale scientists investigated whether SARS-CoV-2 infection could induce amyloid beta buildup similar to what is observed in Alzheimer’s. To do this, they used donated human retinal tissue and created retinal organoids—miniature, lab-grown models of the human retina—that mimic Alzheimer’s pathology by producing more amyloid beta due to genetic mutations.

The researchers confirmed that amyloid beta accumulation occurs in retinal tissues, making the retina a valuable window for studying neurological changes non-invasively. They also identified that SARS-CoV-2 can enter retinal cells by assessing proteins like neuropilin-1 (NRP1) and angiotensin-converting enzyme 2 (ACE2), which facilitate viral entry. Significantly, they detected NRP1 in retinal neurons and glia, indicating a pathway for the virus to invade the eye.

Exposing retinal organoids to the SARS-CoV-2 spike protein resulted in increased amyloid beta levels within the tissues. Moreover, retinal tissues from individuals who had COVID-19, but without a history of dementia, also showed elevated amyloid beta similar to levels in Alzheimer’s disease cases. Importantly, this accumulation was reversible when NRP1 inhibitors were applied, highlighting NRP1 as a potential target for preventing or treating virus-induced neurological damage.

This research suggests that SARS-CoV-2 may contribute to Alzheimer’s-like pathology by promoting amyloid beta aggregation in the retina, a process that could underlie some neurological symptoms seen in COVID-19 patients, such as brain fog. The findings bolster the hypothesis that amyloid beta has antimicrobial properties and that infections could play a critical role in Alzheimer’s disease development.

Future investigations are planned to explore whether early intervention targeting NRP1 or other virus-host interactions could prevent long-term neurological consequences of COVID-19. This line of research opens promising avenues for therapies aimed at mitigating viral-triggered neurodegeneration and underscores the importance of understanding infectious contributions to Alzheimer’s pathology.