A blood-based DNA damage signature in patients with Parkinson's disease is associated with disease progression.

Daisy Sproviero, César Payán-Gómez, Chiara Milanese, Sander Barnhoorn, Shixiang Sun, Akos Gyenis, Domenico Delia, Tammaryn Lashley, Jan H J Hoeijmakers, Jan Vijg, Pier G Mastroberardino

IFOM-ETS, The AIRC Institute of Molecular Oncology, Milan, Italy.IFOM-ETS, The AIRC Institute of Molecular Oncology, Milan, Italy. · pubmed

Paper

Abstract

Aging is the main risk factor for Parkinson's disease (PD), yet our understanding of how age-related mechanisms contribute to PD pathophysiology remains limited. We conducted a longitudinal analysis of blood samples from the Parkinson's Progression Markers Initiative cohort to investigate DNA damage in PD. Patients with PD exhibited disrupted DNA repair pathways and biased suppression of longer transcripts, indicating age-related, transcription-stalling DNA damage. Notably, at the intake visit, this DNA damage signature was detected only in patients with more severe progression of motor symptoms over 3 years, suggesting its potential as a predictor of disease severity. We validated this signature in independent PD cohorts and confirmed increased DNA damage in peripheral blood cells and dopamine neurons of the substantia nigra pars compacta in postmortem PD brains. Our study sheds light on an aging-related mechanism in PD pathogenesis and identifies potential markers of disease progression, providing a diagnostic platform to prognosticate disease progression.

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Research summary

The paper claims that a blood-based DNA damage signature can predict disease severity in Parkinson's disease. This research is relevant as it explores an aging-related mechanism in the pathogenesis of Parkinson's disease, linking DNA damage to disease progression and potentially offering insights into age-related diseases.

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