2026-01-29 チャルマース工科大学
<関連情報>
- https://news.cision.com/chalmers/r/early-signs-of-parkinson-s-can-be-identified-in-the-blood,c4298426
- https://www.nature.com/articles/s41531-025-01194-7
パーキンソン病の前駆期と既往期におけるDNA修復シグネチャー軌跡の縦断的評価 Longitudinal assessment of DNA repair signature trajectory in prodromal versus established Parkinson’s disease
Danish Anwer,Nicola Pietro Montaldo,Elva Maria Novoa-del-Toro,Diana Domanska,Hilde Loge Nilsen & Annikka Polster
npj Parkinson’s Disease Published:05 December 2025
DOI:https://doi.org/10.1038/s41531-025-01194-7
Abstract
Parkinson’s disease (PD) is a progressive neurodegenerative disorder. DNA repair dysfunction and integrated stress response (ISR) dysregulation have been implicated in PD pathophysiology, however, their role during the prodromal phase remains unclear. We analyzed longitudinal blood transcriptomic data from the Parkinson’s Progression Markers Initiative to assess DNA repair and ISR genes in healthy individuals, prodromal PD, and those with established PD. Logistic regression classifiers showed that DNA repair and ISR expression distinguished prodromal PD from healthy individuals, with accuracy peaking in later prodromal stages. In contrast, these pathways did not separate established PD from controls, suggesting a more prominent role early in progression. Gene expression variability in prodromal PD was high at baseline but decreased over time, indicating convergence as disease advances. Notably, 50% of DNA repair genes and 74% of ISR genes showed non-linear patterns, suggesting a transient adaptive response fading with progression. Feature importance analysis highlighted several predictors of prodromal PD, including ERCC6, PRIMPOL, NEIL2, and NTHL1. These findings indicate that DNA repair and ISR dysregulation are relevant in prodromal PD and may be biomarkers for early detection and intervention. Future research should validate these results in larger cohorts and evaluate diagnostic and therapeutic potential.
