Eloy Rodríguez Rodríguez
Head of the Neurology Department at the Marqués de Valdecilla-IDIVAL University Hospital and Associate Professor of Medicine in the Department of Medicine and Psychiatry at the University of Cantabria
This is a basic research article that uses retinal samples from autopsies and in vivo models (organoids) to study the accumulation of beta-amyloid (BA) related to SARS-CoV-2 infection. In my opinion, it draws somewhat pretentious conclusions that are highly debatable.
On the one hand, it demonstrates the presence of higher BA deposits in the retinas of patients who died with COVID-19 and compares them with controls without dementia and with Alzheimer's, obtaining higher concentrations than in healthy controls but lower than in Alzheimer's. The main limitation is that there are only 3-4 subjects per group and the characteristics of the patients are not described. How do we know they did not have dementia? How long had they had COVID-19 when they died? Were there other comorbidities? How many of the controls and people with Alzheimer's had previously had COVID-19? This, especially with such a small number of people, may influence the results.
Next, they exposed organoids to one of the SARS-CoV-2 proteins (not to the actual infection) and observed higher BA production compared to unexposed controls. It should not be forgotten here that one of the physiological functions that has been postulated for BA is its ‘antimicrobial’ action and its role as a participant in innate brain immunity, so we may be seeing a physiological response similar to that which would occur upon exposure to any other virus. It would have been interesting to repeat this experiment with exposure to other viruses, perhaps not so widely reported in the media at present (herpes simplex virus, influenza, Epstein Barr virus, etc.), and see if there are any differences between them.
From all this, they draw the conclusion, which I believe to be hasty, that the retina is useful for studying patients with long COVID, a condition that is still poorly defined and which they have not studied (these are cases of ‘acute’ COVID). In addition, they discuss the role of SARS-CoV-2 as a risk factor for Alzheimer's disease. In this regard, the article provides further evidence of the role that viruses (not only SARS-CoV-2) may play in the pathogenesis of Alzheimer's disease as factors that increase AB production. Most interestingly, it shows that this increase in AB production can be mitigated by blocking a protein that mediates this reaction.
In summary, the article has some methodological shortcomings that I think are important to consider when drawing conclusions from the article. I find the authors' conclusions to be pretentious. Even so, they are further evidence pointing to the role that viruses play in the pathogenesis of Alzheimer's disease, for which there is already experimental evidence.
Regarding the possibility of a future Alzheimer's ‘pandemic’ related to the increased risk conferred by SARS-CoV-2 infection, it is necessary to be alert to an increase in incidence in the coming years, but its effect at the population level is likely to be similar to that of other known viral infections that are ‘commonplace’. At the individual level, there may be individuals in whom this or other infections trigger or accelerate neurodegenerative processes. In this regard, it is still too early to have solid evidence, as more years of observation will be needed, given that these are slow-evolving phenomena.