Abstract

BACKGROUND: Recent epidemiological datasets have associated viral encephalitis exposure (i.e., viral-induced neuroinflammation) with increased risk of Alzheimer’s disease (AD) and dementia, highlighting the need to uncover how it may impact AD neuropathology.

METHODS: Aged 5xFAD and wildtype (WT) mice were infected with JHMV, a neurotropic strain of murine coronavirus to comprehensively determine how coronavirus-induced encephalitis may induce molecular and cellular changes that impact Aβ neuropathology.

RESULTS: JHMV-induced encephalitis at 12 days post-infection resulted in minimal changes to overall Aβ protein, despite increased CD4⁺ and CD8⁺ T cell infiltration and Lgals3/MAC2-expressing macrophages surrounding more compact Aβ plaques in the brain. Spatial transcriptomic imaging and pathway analysis of differentially expressed genes (DEGs) within myeloid cells demonstrate down-regulated disease-associated (DAM) pathways involving Aβ clearance, response to lipids, and macrophage activation within infected 5xFAD brains.

CONCLUSIONS: JHMV encephalitis induces dysregulated gene expression and myeloid cell responses to Aβ plaque burden in 5xFAD mouse brains.