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2022 Alzheimer's Association Research Fellowship to Promote Diversity (AARF-D)

Brain Misfolded Protein Aggregation Due to SARS-CoV-2 Infection.

What may be the biological underpinnings that link COVID-19 and Alzheimer’s disease related brain changes?

Nicolas Bravo Vasquez, Ph.D., D.V.M.
The University of Texas Health Science Center at Houston
Houston, TX - United States


Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for COVID-19, has infected more than 200 million individuals worldwide since 2019. Although still unclear, some studies suggest that SARS-CoV-2 may damage nerve cells and other brain components, although it is unclear if this is direct (by getting into the brain) or indirect (acting outside the brain) or both (direct and indirect). The virus may trigger and promote the accumulation of misshapen (or “misfolded”) brain proteins linked to Alzheimer’s and related dementia. These misfolded proteins include beta-amyloid plaques and tau tangles, two hallmark brain changes associated with Alzheimer’s.  Scientists, however, remain uncertain how SARS-CoV-2 interacts with the brain and how this interaction may impact Alzheimer’s-related brain changes.

Research Plan

Dr. Nicolas Bravo Vasquez and colleagues will study the possible role of SARS-CoV-2 in Alzheimer’s and related dementias. They will do this using the brains of individuals who either had or did not have COVID-19. They will measure levels of abnormal tau, beta-amyloid and other misfolded proteins in the brain to  assess how the presence of SARS-CoV-2 impacted these protein levels. 

Next, they will develop a three-dimensional brain-like structure (called a brain organoid) that closely resembles the brains of individuals with SARS-CoV-2 infection. This brain organoid will be created in the laboratory from induced pluripotent stem cells (iPSCs), which are stem cells engineered from adult human skin cells and then “reprogrammed” into brain cells. Dr. Bravo Vasquez’ team will investigate how SARS-CoV-2 may affect the accumulation of misfolded proteins. The goal will be to understand how these changes contribute to downstream biological changes including brain cell death, the loss of cell-to-cell communication and other dementia-related brain changes.     


Results from this project could improve our understanding of how SARS-CoV-2  impacts brain health. They could also suggest novel strategies for preventing or treating COVID-related brain damage. Such findings may prove vital as new COVID-19 variants continue to impact people around the world.

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