Single-cell analysis of Powassan virus-infected brains reveals age-dependent neuroinflammatory crosstalk and progressive Alzheimer's-like APP/Aβ accumulation.

Powassan virus infection causes age-dependent neuroinflammation and persistent Alzheimer’s-like APP/Aβ accumulation in mouse brains, with 50-week-old mice showing significant neurodegenerative changes.

• Why it matters: Understanding how POWV leads to long-term neurological deficits is crucial, as survivors often experience cognitive decline, yet the mechanisms remain unclear. This research addresses the gap in knowledge about age-related differences in disease progression and neurodegeneration caused by POWV.
• What they did: Single-cell RNA sequencing was used to analyze CNS responses in young (10-week-old) and aged (50-week-old) mice infected with POWV LI9, revealing distinct immune and glial responses, including APP/Aβ accumulation and microglial activation linked to Alzheimer’s disease pathways.
• The result: POWV triggers neurodegenerative microglial states and persistent APP/Aβ buildup, suggesting the virus may initiate or worsen Alzheimer’s-like pathology, which could explain long-term neurological sequelae in human survivors and inform future therapeutic strategies.