CLEVELAND — A new study led by the Cleveland Clinic has identified mechanisms by which COVID-19 can cause Alzheimer’s disease-like dementia.
The findings, published in Alzheimer’s Research & Therapy, show a link between COVID-19 and brain changes associated with Alzheimer’s disease. They could help inform risk management and therapeutic strategies for COVID-19-associated cognitive impairment.
Reports of neurological complications in COVID-19 patients and “long-hauler” patients whose symptoms persist after the infection clears are becoming more common, implying that SARS-CoV-2, the virus that causes COVID-19, may have long-term effects on brain function.
However, it is unclear how the virus causes neurological problems.
“While some studies suggest that SARS-CoV-2 infects brain cells directly, others found no evidence of the virus in the brain. Identifying how COVID-19 and neurological problems are linked will be critical for developing effective preventive and therapeutic strategies to address the surge in neurocognitive impairments that we expect to see in the near future,” said Feixiong Cheng, Ph.D., assistant staff in Cleveland Clinic’s Genomic Medicine Institute and lead author on the study
Using existing datasets of Alzheimer’s patients and COVID-19, the researchers used artificial intelligence in the study. They calculated the distance between SARS-CoV-2 host proteins and those linked to various neurological diseases, with closer proximity indicating related or shared disease pathways. The scientists also looked at the genetic factors that allowed the virus to infect brain tissues and cells.
While there is little evidence that the virus directly targets the brain, researchers discovered close network relationships between the virus and genes associated with several neurological diseases pointing to pathways through which COVID-19 could cause Alzheimer’s disease-like dementia.
To delve deeper, they looked into possible links between COVID-19 and neuroinflammation and microvascular brain injury, both of which are hallmarks of Alzheimer’s.
“We discovered that SARS-CoV-2 infection significantly altered Alzheimer’s markers implicated in brain inflammation and that certain viral entry factors are highly expressed in cells in the blood-brain barrier. These findings indicate that the virus may impact several genes or pathways involved in neuroinflammation and brain microvascular injury, which could lead to Alzheimer’s disease-like cognitive impairment,” added Dr. Cheng.
The researchers also discovered that people with the APOE E4/E4 allele, the most common genetic risk factor for Alzheimer’s, had lower expression of antiviral defense genes, making them more vulnerable to COVID-19.
“Ultimately, we hope to have paved the way for research that leads to testable and measurable biomarkers that can identify patients at the highest risk for neurological complications with COVID-19,” said Dr. Cheng.
Dr. Cheng and his colleagues are currently using cutting-edge network medicine and artificial intelligence technologies to identify actionable biomarkers and new therapeutic targets for COVID-19-related neurological issues in “long-hauler” sufferers.