Findings from a small sample of those who died from the virus indicate that their ryanodine receptors were affected.
The brains of a small sample individuals who died of COVID-19 displayed some of the same molecular changes found in the brains of individuals with Alzheimer disease (AD), results of a study from Columbia University Vagelos College of Physicians and Surgeons show.
The findings, published in Alzheimer's & Dementia: The Journal of the Alzheimer's Association, could help explain the memory issues reported by individuals with long COVID-19. However, investigators cautioned that the study is small.
The data pool only included 10 individuals, and investigators said the study should be replicated by others.
Early reports of a feeling of so-called brain fog and persistent cardiac symptoms in individuals who recovered from COVID-19 prompted the investigators to explore how certain molecules called ryanodine receptors are affected by the disease.
Defective ryanodine receptors have been implicated in diverse pathogenic processes, including AD, the brain response to stress, and heart and lung disease, investigators said.
"When the COVID pandemic hit, like everybody else I was interested in being helpful and doing what we could do," Andrew Marks, MD, chair of the department of physiology and cellular biophysics at the Vagelos College of Physicians and Surgeons, said in a statement.
"What we found is really I think quite unexpected,” he said. “Not only did we find defective ryanodine receptors in the hearts and lungs of deceased COVID patients, we also found them in their brains.
Inside neurons, defective ryanodine receptors have been linked to an increase in phosphorylated tau, a hallmark of AD.
In the new study, investigators found high levels of phosphorylated tau in the brains of individuals with COVID-19.
Phosphorylated tau was found in areas where they are typically located in individuals with AD, as well as in areas where tau was not typically located in individuals with AD. This suggests that phosphorylated tau in individuals with COVID-19 could be a sign of early-stage AD and contribute to other neurological symptoms observed in individuals with COVID-19.
Increased levels of phosphorylated tau in the brain are thought to be linked to memory problems in AD and could be causing similar issues in individuals with long COVID-19, Marks said.
Based on the findings and additional changes found in the brain, investigators theorized that the immune response characteristic of severe COVID-19 causes inflammation in the brain. In turn, this could lead to dysfunctional ryanodine receptors and then to increases in phosphorylated tau.
No changes were found in the pathways that lead to the formation of amyloid beta, another hallmark of AD.
"One interpretation of these findings is that long COVID could be an atypical form of Alzheimer's and/or that patients who had severe COVID could be predisposed to developing Alzheimer's later in life. But much more research needs to be done before we can make more definitive conclusions,” Marks said.
If the memory and neurological problems of long COVID-19 can be traced to defective ryanodine receptors, a drug in the early stages of clinical trials, developed by Marks, could help.
The drug would be used to treat muscle disease caused by an inherited defect in the ryanodine receptor. The drug was able to fix the ryanodine defect when applied to the brain tissue of the individuals with COVID-19.
Small study finds Alzheimer's-like changes in some COVID patients' brains. Science Daily. News release. February 3, 2022. Accessed February 8, 2022. https://www.sciencedaily.com/releases/2022/02/220203122947.htm