Viral Infection Induces Alzheimer’s Disease-Related Pathways and Senescence in iPSC-Derived Neuronal Models

INTRODUCTION: The Pathogen Infection Hypothesis proposes that β-Amyloid (Aβ) functions as an antimicrobial peptide, with pathogen-induced aggregation potentially contributing to Alzheimer's disease (AD) pathology. METHODS: mutant) lines to model acute infections with HSV-1 and TBEV and Aβ aggregation. Transcriptomic and proteomic analyses were conducted to assess molecular responses. RESULTS: mutations did not alter the acute infection response. Reanalysis of independent datasets confirmed our findings and revealed a limited protective effect of acyclovir. DISCUSSION: Results directly support the Pathogen Infection Hypothesis and suggest that preventing viral infections via vaccinations may represent a feasible approach to reducing AD risk.