Blood biomarkers may identify Parkinson's before symptoms appear

Different patterns of gene expression have been detected in blood samples in the earliest stage of Parkinson's disease.

Parkinson's disease is a neurodegenerative movement disorder that currently has no cure. There can be several decades between pathological disease onset and the occurrence of movement symptoms which prompt clinical diagnosis, often called the prodromal stage. By the time of diagnosis, extensive damage to the brain has already occurred. Therefore, detection of people in the prodromal stage offers a window of opportunity for disease-modifying interventions prior to extensive brain damage. Now, researchers have identified changes in DNA repair and integrated stress response pathways that distinguished prodromal Parkinson's from healthy individuals, which could be biomarkers for earlier detection of the disease.

'In our study, we highlighted biomarkers that likely reflect some of the early biology of the disease and showed they can be measured in blood. This paves the way for broad screening tests via blood samples: a cost-effective, easily accessible method' said Dr Annikka Polster from Chalmers University of Technology, Sweden, who led the study. 'If we can study the mechanisms as they happen, it could provide important keys to understanding how they can be stopped and which drugs might be effective.'

Published in npj Parkinson's disease, researchers analysed transcriptomic data from blood samples at four timepoints over three years, collected as part of the pre-existing Parkinson's Progression Markers Initiative study. They compared samples from 393 people diagnosed with Parkinson's disease, 58 people with prodromal Parkinson's disease (who do not yet show movement symptoms of Parkinson's but have other symptoms that suggest they are at risk of developing Parkinson's in the future) and 188 healthy controls.

Using machine learning algorithms, they identified longitudinal patterns of gene expression related to nuclear DNA damage repair, mitochondrial DNA damage repair and integrated stress response pathways which distinguished those with prodromal Parkinson's disease from healthy controls, but failed to reliably distinguish established Parkinson's disease and healthy controls groups. Feature importance analysis highlighted specific DNA repair genes as significant molecular predictors of prodromal Parkinson's, including ERCC6, PRIMPOL, NEIL2, and NTHL1.

They also found highly variable gene expression early in prodromal Parkinson's and dynamic, non-linear trajectories in 50 percent of DNA repair genes and 74 percent of integrated stress response genes, in contrast with the relatively stable gene expression in established Parkinson's and healthy control groups. This may suggest an initial adaptive response aimed at mitigating accumulating molecular stress that becomes less active as the disease progresses.

Further research is needed to develop a test to measure these specific molecular patterns in the blood in future clinical settings.