Cortical-blood vessel assembloids exhibit Alzheimer's disease pathologies by activating glia after SARS-CoV-2 infection

ABSTRACT

A correlation between COVID-19 and Alzheimer's disease (AD) has been proposed recently. Although the number of case reports on neuroinflammation in COVID-19 patients has increased, studies of SARSCoV- 2 neurotrophic pathology using brain organoids have restricted recapitulation of those phenotypes due to insufficiency of immune cells and absence of vasculature. To overcome these limitations, we developed fused cortical-blood vessel organoids to provide blood vessels to brain organoids and obtained the characteristics of increased expression of glial cells and blood-brain barrier-like structures in brain organoids. Furthermore, we observed AD pathologies, including Abeta plaques, which were affected by the inflammatory response from SARS-CoV-2 infection. These findings provide an advanced platform to investigate human neurotrophic diseases, including COVID-19, and suggest that neuroinflammation caused by viral infection facilitates AD pathology.