biostudies-literatureGreen RBLRD VANCI NIH HHSNINDS NIH HHS217-229https://www.ebi.ac.uk/biostudies/studies/S-EPMC9508696biostudies-literatureUnknown27The 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 <i>Ifi204</i>, 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.Molecular therapy. Methods & clinical developmentSARS-CoV-2 infection increases the gene expression profile for Alzheimer's disease risk.PMC9508696R01 NS073899IK6 BX004214IK6 BX004212I01 BX005490R01 CA180758I01 BX005757I01 BX004626Chandran BMohapatra SGreen RMayilsamy KMohapatra SSMartinez TEMcGill ARBickford PCBlair LJfalseSARS-CoV-2 infection increases the gene expression profile for Alzheimer's disease risk.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 <i>Ifi204</i>, 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.2022-01-01T00:00:00Z2022 Dec2026-05-28T06:36:58.994Z2024-11-07T00:36:52.396ZS-EPMC95086963618772010.1016/j.omtm.2022.09.007