SARS-CoV-2 infection increases the gene expression profile for Alzheimer's disease risk.

Abstract

The coronavirus disease 2019 (COVID-19) pandemic has caused over 600,000,000 infections globally thus far. Up to 30% of individuals with mild to severe disease develop long COVID, exhibiting diverse neurologic symptoms including dementias. However, there is a paucity of knowledge of molecular brain markers and whether these can precipitate the onset of Alzheimer's disease (AD). Herein, we report the brain gene expression profiles of severe COVID-19 patients showing increased expression of innate immune response genes and genes implicated in AD pathogenesis. The use of a mouse-adapted strain of SARS-CoV-2 (MA10) in an aged mouse model shows evidence of viral neurotropism, prolonged viral infection, increased expression of tau aggregator FKBP51, interferon-inducible gene Ifi204, and complement genes C4 and C5AR1. Brain histopathology shows AD signatures including increased tau-phosphorylation, tau-oligomerization, and α-synuclein expression in aged MA10 infected mice. The results of gene expression profiling of SARS-CoV-2-infected and AD brains and studies in the MA10 aged mouse model taken together, for the first time provide evidence suggesting that SARS-CoV-2 infection alters expression of genes in the brain associated with the development of AD. Future studies of common molecular markers in SARS-CoV-2 infection and AD could be useful for developing novel therapies targeting AD.

• Authors: Ryan Green, Karthick Mayilsamy, Andrew R McGill, Taylor E Martinez, Bala Chandran, Laura J Blair, Paula C Bickford, Shyam S Mohapatra, Subhra Mohapatra
• Journal: Molecular therapy. Methods & clinical development (Mol Ther Methods Clin Dev) Vol. 27 Pg. 217-229 (Dec 08 2022) ISSN: 2329-0501 [Print] United States
• PMID: 36187720 (Publication Type: Journal Article)