Cortical-blood Vessel Assembloids Exhibit Alzheimer's Disease Phenotypes by Activating Glia After SARS-CoV-2 Infection

Overview

Journal Cell Death Discov

Date 2023 Jan 25

PMID 36697403

Authors

Dasom Kong

Ki Hoon Park

Da-Hyun Kim

Nam Gyo Kim

Seung-Eun Lee

Nari Shin

Myung Geun Kook

Young Bong Kim

Kyung-Sun Kang

Affiliations

Soon will be listed here.

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 SARS-CoV-2 neurotrophic pathology using brain organoids have restricted recapitulation of those phenotypes due to insufficiency of immune cells and absence of vasculature. Cerebral pericytes and endothelial cells, the major components of blood-brain barrier, express viral entry receptors for SARS-CoV-2 and response to systemic inflammation including direct cell death. To overcome the limitations, we developed cortical-blood vessel assembloids by fusing cortical organoid with blood vessel organoid to provide vasculature to brain organoids a nd obtained the characteristics of increased expression of microglia and astrocytes in brain organoids. Furthermore, we observed AD pathologies, including β-amyloid 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.

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