Early Blood Test May Predict Parkinson’s Disease Decades Before Symptoms
Annikka Polster, Nicola Montaldo and Hilde Nilsen, from the Genome instability in disease and ageing group at OUS, has together with their collaborators identified a blood-based “signature” that may reveal Parkinson’s disease (PD) 10–20 years before classic motor symptoms like tremors and stiffness appear. The results were recently published in NPJ Parkinson’s Disease.
The Challenge of Late Diagnosis
Parkinson’s is usually diagnosed only after many of the brain cells that control movement are already lost. This study asked whether early molecular warning signs can be detected in the blood long before diagnosis. The researchers focused on genes involved in repairing damaged DNA and in the “integrated stress response” (ISR), a cellular alarm system that helps cells cope with stress.
Searching for Early Molecular Warning Signs
Using repeated blood samples from participants in the large international Parkinson's Progression Markers Initiative (PPMI), supported by the Michael J. Fox Foundation, they analyzed RNA sequencing data from healthy individuals, people in a prodromal (pre-diagnosis) phase of PD, and patients with established PD. Machine learning models were trained to detect specific patterns of gene activity.
A Distinct Blood Signature in Early Parkinson’s
The team found that patterns of DNA repair and ISR gene expression clearly distinguished individuals in the prodromal phase of PD from healthy controls, with up to about 90% accuracy at later prodromal time points. By contrast, these patterns could not reliably separate patients with established PD from healthy individuals. Early in the prodromal phase, gene expression was highly variable, and many genes showed non-linear “rise and fall” trajectories, suggesting a temporary, adaptive self-defense phase in which cells try to repair damage before too many nerve cells in the brain are lost.
Towards a Diagnostic Blood Test
This “stress response” blood signature appears to be present only in people in the early, prodromal stage of Parkinson’s, not in patients with established disease or in healthy controls. This points to a limited but crucial window for early detection and intervention. The researchers hope to develop this signature into a diagnostic blood test that could be used in routine health care within about five years, assuming sufficient funding and access to biological samples. Earlier diagnosis would allow treatment to begin while patients still have more functioning nerve cells, potentially increasing the chances of slowing or even halting disease progression.
Links:
Hilde Nilsen’s research group:
OUH - Genome instability in disease and ageing
Nicola Montalto’s group:
OUH - Mitonuclear DNA Maintenance and Transcriptional Control
Annikka Polsters lab:
https://www.sysbio.se/labs/polster-lab/
Link to the paper:
Longitudinal assessment of DNA repair signature trajectory in prodromal versus established Parkinson’s disease | npj Parkinson's Disease