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

ABSTRACT:

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

We used human iPSC-derived 2D neurons and 3D cerebral organoids from wild-type and familial AD (PSEN1/2 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

HSV-1, but not TBEV, induced robust Aβ clustering, which was, however, dependent on extracellular amyloid peptides. Transcriptomic profiling revealed widespread HSV-1-induced changes, including activation of neurodegeneration-related pathways. Proteomic profiling confirmed

SUBMITTER: Hribkova H 

PROVIDER: S-EPMC12259118 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature