Network meta-analysis on alcohol-mediated modulation of Alzheimer’s disease in the diseases of inflammation including COVID-19

Abstract

Objectives Cross sectional surveys have reported that alcohol consumption has skyrocketed during the COVID-19 pandemic. Chronic alcohol use triggers systemic inflammation which leads to neuroinflammation and neurodegeneration. In the present study, we hypothesize that alcohol consumption and cytokine elevation during inflammatory conditions synergistically increase amyloid-beta precursor protein (APP) expression and worsens Alzheimer’s disease (AD) pathology. Methods QIAGEN Ingenuity Pathway Analysis (IPA) was employed to conduct network meta-analysis on the molecular mechanisms underlying ethanol (EtOH) influence on APP expression and AD in inflammatory conditions including COVID-19, inflammation of respiratory system, organ, absolute anatomical region, body cavity, joint, respiratory system component, gastrointestinal tract, large intestine, liver, central nerve system, and lung. IPA tools were utilized to identify the molecules associated with EtOH, inflammatory conditions and the common molecules between them. Results Simulation activity of EtOH, mimicking exposure to alcohol, upregulated the APP expression and augmented AD pathology in all inflammatory conditions including COVID-19. Our studies identified six molecules including ADORA2A, Cytokine, IFN-gamma, IL1-beta, Immunoglobulin and TNF, which concurrently contribute to increased APP expression and AD progression upon EtOH simulation in all diseases studied. Conclusions The present study has revealed molecular mechanisms underlying alcohol augmentation of AD in COVID-19 and other diseases of inflammation.

Network meta‐analysis of the molecular mechanisms and signaling pathways underlying alcohol‐induced thymic atrophy

“…The “Downstream Effect Analysis” was performed to determine the contribution of each intermediating molecule following EtOH simulation on thymic atrophy as previously reported (Bishir et al., 2023; Huang et al., 2021; Zhang et al., 2023) using the formula reported by Krämer et al. (2014).…”