Alzheimer’s gene linked to COVID-19 risk

The gene that increases the risk of Alzheimer's disease can increase a person's susceptibility to and severity of COVID-19, researchers say.

The study, published in journal 'Cell Stem Cell', suggests that the gene -- ApoE4 -- showed a higher susceptibility to SARS-CoV-2 infection.

"Our study provides a causal link between the Alzheimer's disease risk factor ApoE4 and Covid-19 and explains why some (e.g., ApoE4 carriers) but not all Covid-19 patients exhibit neurological manifestations," researcher Yanhong Shi from the US City of Hope said.

"Understanding how risk factors for neurodegenerative diseases impact COVID-19 susceptibility and severity will help us to better cope with COVID-19 and its potential long-term effects in different patient populations," Shi added.

For the study, the team first created brain cells in the lab using pluripotent stem cells (iPSCs), which are a kind of stem cell that can become virtually any type of cell.

The newly created neurons and astrocytes, a type of helper cell, were then infected with SARS-CoV-2. They found that both cell types were susceptible to infection.

Next, the team used iPSCs to create brain organoids, which are 3D tissue models that mimic certain features of the human brain.

They created one organiod model that contained astrocytes and one without them. They then infected both brain organoid types with the virus, and discovered that those with astrocytes boosted SARS-CoV-2 infection.

The team went on to further study the effects of ApoE4 on susceptibility to SARS-CoV-2 by generating neurons from iPSCs "reprogrammed" from the cells of an Alzheimer's patient that contained ApoE4.

Using gene editing, the team modified some of the iPSCs-created ApoE4 cells so that they contained ApoE3, which is a gene type that is considered neutral. The ApoE3 and ApoE4 iPSCs were then used to generate neurons and astrocytes.

The ApoE4 neurons and astrocytes both showed a higher susceptibility to SARS-CoV-2 infection in comparison to the neutral ApoE3 neurons and astrocytes.

In the last part of the study, the researchers tested to see if the antiviral drug remdesivir inhibits virus infection in neurons and astrocytes. They discovered that the drug was able to successfully reduce the viral level in astrocytes and prevent cell death.