# Aberrant Cell Cycle Gene Expression in a Transgenic Mouse Model of Alzheimer’s Disease

## TL;DR

This study finds that genes related to the cell cycle are dysregulated in a mouse model of Alzheimer’s disease, suggesting these changes may contribute to neurodegeneration.

## Contribution

The study provides the first systematic analysis of cell cycle gene dysregulation in aged APP/PS1 mice and identifies potential miRNA regulators.

## Key findings

- 32 cell cycle-related genes were differentially expressed in aged APP/PS1 mice brains.
- 8 genes showed significant changes (fold change > 2, p < 0.05) and were also dysregulated in human AD brains.
- miRNA prediction analyses identified candidate post-transcriptional regulators of these genes.

## Abstract

Alzheimer’s disease (AD) is increasingly recognized as a disorder that extends beyond amyloid-β (Aβ) and tau pathology. To this end, growing evidence suggests that aberrant neuronal cell cycle re-entry (CCR) may contribute to neurodegeneration. To investigate this mechanism, we profiled the expression of 84 cell cycle-related genes in the brains of aged APP/PS1 mice, a widely used transgenic model of AD, and compared them with age-matched non-transgenic littermates. Our analysis revealed 32 differentially expressed genes (DEGs), 8 of which exhibited significant changes (fold change > 2, p < 0.05). Several of these DEGs, including CDC7 and CCNC, displayed consistent dysregulation in human AD brains as assessed using the AMP-AD knowledge portal, supporting their translational relevance. Furthermore, integration with miRNA prediction analyses identified candidate post-transcriptional regulators of these DEGs, highlighting novel layers of regulation. Collectively, our results provide the first systematic overview of cell cycle gene dysregulation in aged APP/PS1 mice, establish cross-species concordance with human AD, and propose miRNA–gene interactions as potential contributors to neuronal vulnerability. These findings underscore the importance of cell cycle pathways in AD pathogenesis and point to new avenues for therapeutic exploration.