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SARS-CoV-2 Infection Increases the Gene Expression Profile for Alzheimer's Disease Risk

COVID-19 is primarily a respiratory disease, however neurological symptoms are also reported in a subpopulation of infected COVID-19 individuals with substantially higher rates, up to 84 per cent in severe COVID-19 cases. For instance, patients with previous severe COVID-19 exhibit a 10-year average drop in their global cognitive performance. Complementary studies combining neuroimaging and cognitive screening implicate COVID-19-induced impairment of the frontal cortex, a critical area for cognitive function. Furthermore, the effects of COVID-19 on the nervous system, including cognitive impairment, are expected to be long-term. While the virus itself is not new, the longevity of these effects and how severe they could be to an individual are unknown.

Older adults infected with COVID-19 are at a greater risk of developing Alzheimer’s disease within a year, according to a new study. Unfortunately, an understanding of mechanisms why COVID-19 can trigger Alzheimer’s disease is lacking.

A recent study published in ‘Molecular Therapy and Clinical Development’ from research conducted during 2021 to 2022 at USF’s Morsani College of Medicine and James A Haley VA Hospital, found that those patients with severe long COVID-19 brains overexpress genes similar to that of Alzheimer’s. The data from these select genes were validated using aged mice infected with a mouse adapted strain of COVID-19 and tracked their brain expression and function. 

“The risk factors that play into the development of Alzheimer’s disease after acute viral infections have been poorly understood, and this is compounded with aging and innate immune inflammation”, said lead author Dr. Subhra Mohapatra, who is the Professor of Molecular Medicine at the USF’s Morsani College of Medicine.   

Bioinformatic studies of changes in gene expression among human brains affected by Alzheimer’s or COVID-19 and the aged mouse model infected with COVID-19 identified common hub genes and pathways like that of Alzheimer’s disease and dementias (see image).  The investigators tested for some of the identified risk genes and reasoned that COVID-19 could infect nerve tissue in aged mouse brains causing innate immune activation, neuro- inflammation, and neurodegeneration. These would then lead to the development of Alzheimer and dementia diseases. In their study, the researchers found that in aged mice, viral infection of COVID-19 was evident in leading to early signs of Alzheimer’s disease.

The complexity of the disease and inability to collect data overtime has made it very difficult to understand the direct causes of the disease. While these studies don’t lead to a discovery linking COVID-19 causing Alzheimer directly, an overlap in gene expressions of both diseases from the study prompts further research. With this study, it creates hope to develop more accurate research for the millions of Americans impacted by Alzheimer diseases.  “This study opens up new avenues to consider therapeutic approaches to attenuate Alzheimer’s disease risk factors in severe COVID and long COVID patients,” said Dr. Shyam Mohapatra, the study co-author and a distinguished Health Professor and Division Director of Translational Medicine at the USF Department of Internal Medicine.  

The other study co-authors include Dr. Ryan Green, a post-doctoral fellow, three doctoral graduate students Karthick Mayilsamy, Andrew R McGill and Taylor Martinez, as well as Dr. Laura J Blair, an Assistant Professor in the USF Health Byrd Institute and Department of Molecular Medicine, Dr. Paula Bickford, a distinguished Professor in the USF Center of Excellence for Aging and Brain Repair and Dr. Bala Chandran, Professor in the USF Department of Molecular Medicine. 

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