February 1, 2022
Written by: Catrina Hacker
Almost two years into the COVID-19 pandemic scientists and doctors have learned a lot about how the disease presents and progresses, culminating in the development of several vaccines as well as a newly-authorized COVID-19 pill1. New research suggests that what we have learned about COVID-19 may also help us understand another disease: Alzheimer’s. Many COVID-19 patients suffer from neurological symptoms (explored in these two previous posts: here and here). As we continue to learn more about exactly how the virus interacts with the brain, several interesting parallels between neurological symptoms of COVID-19 infection and the progression of Alzheimer’s disease have been uncovered2,3.
Six million Americans are currently living with Alzheimer’s, and that number is expected to more than double by 20504, making the development of treatments and a possible cure for Alzheimer’s a matter of the utmost urgency. Our current understanding of Alzheimer’s centers around two proteins: beta-amyloid and tau. Scientists believe that Alzheimer’s starts with the accumulation of a protein called beta-amyloid in a region of the brain called the hippocampus, which is responsible for memory formation. This beta-amyloid clumps into plaques that trigger the formation of tau proteins inside of neurons, disrupting the neurons’ ability to function properly5. While there is much scientific evidence that these proteins are present in abnormally high quantities in the brains of patients with Alzheimer’s, recent therapies that attempt to clear these protein plaques did not relieve cognitive symptoms6,7. This suggests a need to look elsewhere to develop more effective treatments.
While most scientists have since turned toward other hypotheses, the idea that Alzheimer’s might be induced by viral, bacterial, or fungal infection was first proposed in 19522. Herpes Virus 1 is found in the brains of almost all elderly people (both healthy patients and those with Alzheimer’s), but more of the virus is present in Alzheimer’s patients’ brains. Several studies have demonstrated that herpesvirus infection can stimulate the production of beta-amyloid, providing a possible link between herpesvirus infection and Alzheimer’s Disease8. Another research group has shown that immune cells in the brain respond to the presence of beta-amyloid in the same way that lung cells respond to the presence of SARS virus2, suggesting that similar treatments might be effective in both cases. Very few active clinical trials focus on antiviral treatments, meaning this could be a useful new line of investigation toward new Alzheimer’s drug treatments.
Severe COVID-19 infection is associated with the development of cognitive symptoms, but how infection causes these symptoms is still not well understood. Thus far, there is mixed evidence about whether SARS COV-2, the virus responsible for COVID-19, is actually present in the brains of patients with COVID-19. One study found that ten out of eleven patients who died of COVID-19 infection had SARS COV-2 present in their brains9. Another study found no SARS COV-2 in the brains of patients with COVID-19, but did find that microglia, an immune cell in the brain, were activated in the same way as in the brains of patients with Alzheimer’s Disease10. Another study found proteins that were previously thought to be specific to Alzheimer’s Disease present in the blood of patients with COVID-1911. Several new studies are starting to examine the response of Alzheimer’s patients to COVID-19 infection to look for more clues about the interaction between these two diseases, but how these two diseases interact remains poorly understood12. There is still a lot to learn about the meaning of these connections between Alzheimer’s Disease and COVID-19, but they offer several promising new leads on possible ways to target and treat Alzheimer’s Disease.
The recent surge of resources toward COVID-19 research has led to unprecedentedly rapid progress in our understanding of the disease. While it wasn’t an intended purpose of this research, the newly-discovered link between COVID-19 and Alzheimer’s Disease has opened up several otherwise under-explored areas of research toward a treatment or cure. Alzheimer’s Disease certainly isn’t the only unexpected place that this investment will provide insight, and we should continue to see the benefits of this investment in research, both basic and translational, for decades to come.
Cover image from Pixabay
1. Commissioner, O. of the. Coronavirus (COVID-19) Update: FDA Authorizes First Oral Antiviral for Treatment of COVID-19. FDA https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-fda-authorizes-first-oral-antiviral-treatment-covid-19 (2021).
2. Yasinski, E. Could viruses cause Alzheimer’s? COVID-19 brain studies offer new clues. National Geographic https://www.nationalgeographic.com/science/article/could-viruses-cause-alzheimers-covid-19-brain-studies-offer-new-clues (2022).
3. Rahman, M. A., Islam, K., Rahman, S. & Alamin, M. Neurobiochemical Cross-talk Between COVID-19 and Alzheimer’s Disease. Mol. Neurobiol. 58, 1017–1023 (2021).
4. Facts and Figures. Alzheimer’s Association https://www.alz.org/alzheimers-dementia/facts-figures.
5. Jack, C. R. et al. Hypothetical model of dynamic biomarkers of the Alzheimer’s pathological cascade. Lancet Neurol. 9, 119–128 (2010).
6. Liu, P.-P., Xie, Y., Meng, X.-Y. & Kang, J.-S. History and progress of hypotheses and clinical trials for Alzheimer’s disease. Signal Transduct. Target. Ther. 4, 29 (2019).
7. Kametani, F. & Hasegawa, M. Reconsideration of Amyloid Hypothesis and Tau Hypothesis in Alzheimer’s Disease. Front. Neurosci. 12, 25 (2018).
8. Wainberg, M. et al. The viral hypothesis: how herpesviruses may contribute to Alzheimer’s disease. Mol. Psychiatry 26, 5476–5480 (2021).
9. Chertow, D. et al. SARS-CoV-2 infection and persistence throughout the human body and brain. https://www.researchsquare.com/article/rs-1139035/v1 (2021) doi:10.21203/rs.3.rs-1139035/v1.
10. Yang, A. C. et al. Dysregulation of brain and choroid plexus cell types in severe COVID-19. Nature 595, 565–571 (2021).
11. Frontera, J. A. et al. Comparison of serum neurodegenerative biomarkers among hospitalized COVID‐19 patients versus non‐COVID subjects with normal cognition, mild cognitive impairment, or Alzheimer’s dementia. Alzheimers Dement. alz.12556 (2022) doi:10.1002/alz.12556.
12. Ciaccio, M. et al. COVID-19 and Alzheimer’s Disease. Brain Sci. 11, 305 (2021).