New study finds early Parkinson’s signals in blood years before symptoms
Protein changes may help identify disease risk long before diagnosis
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- Parkinson’s-related biological changes, including inflammation, may appear up to 12 years before diagnosis.
- Blood tests identified protein changes (ITGAV, VCAM1, CXCL12) linked to future Parkinson’s risk.
- Identifying early biomarkers may help detect disease sooner and guide efforts to slow progression.
Biological changes associated with Parkinson’s disease, including newly identified changes in a signaling network linked to neuroinflammation, or brain inflammation, may begin up to 12 years before diagnosis.
That’s according to data from a proof-of-concept study of Grifols’ Chronos-PD research initiative, which aims to identify biomarkers that can help predict disease risk and guide future treatments by combining blood samples collected over 15 years with advanced protein analyses and artificial intelligence (AI).
Study tracks biological changes years before Parkinson’s diagnosis
The findings were announced in a company press release and presented at the AD/PD Alzheimer’s & Parkinson’s Diseases Conference, held March 17-21, in Copenhagen, Denmark.
Results have also been made available online as a preprint of the study, titled “Early Parkinson’s Revealed by Unlocking Longitudinal Omics at Population Scale,” which has not yet been published in a peer-reviewed journal.
“This new proof-of-concept data offers additional insights into the biology and progression of PD [Parkinson’s disease], years before clinical detection,” said Jörg Schüttrumpf, Grifols’ chief scientific innovation officer. “Going back in time to search for the earliest signs of disease can help accelerate and ultimately develop new diagnostics and disease-modifying therapeutics.”
Parkinson’s is caused by the progressive loss of dopaminergic neurons, the nerve cells that produce the signaling molecule dopamine. The accumulation of toxic clumps of alpha-synuclein protein and neuroinflammation are thought to contribute to disease development and progression.
Currently, Parkinson’s is diagnosed after symptoms begin, based on medical history, physical examination, and brain imaging tests. By the time Parkinson’s is diagnosed, substantial nerve cell loss has often already occurred, limiting opportunities for early intervention.
Thus, early disease biomarkers may help detect disease before symptoms begin and support the development of earlier interventions. Identifying these biomarkers before symptoms appear may help improve diagnosis and guide efforts to slow disease progression in Parkinson’s patients.
Large dataset helps map disease-related changes over time
Chronos-PD is a pioneering program driven by Grifols’ subsidiary Alkahest. Researchers are drawing on a repository of more than 100 million blood samples and matching them with real-world data to identify molecular changes that occur years before a clinical diagnosis of Parkinson’s.
In this proof-of-concept study, funded by the Michael J. Fox Foundation for Parkinson’s Research (MJFF), researchers analyzed 2,609 blood samples from 348 individuals with Parkinson’s and 348 matched controls, spanning up to 12 years before and nine years after disease diagnosis.
Proteins were identified using four proteomic platforms, or advanced technologies used for large-scale identification, measurement, and analysis of proteins. Across these platforms, 7.1% to 26% of proteins had also been reported in previous Parkinson’s studies.
Among 1,748 samples from 481 individuals, including both patients and controls, obtained before disease onset, 12 proteins with altered levels were identified. Pathway analysis suggested these proteins were linked to nerve cell pathways, immune cell activation, and cell adhesion, such as integrin subunit alpha V (ITGAV) and vascular cell adhesion molecule-1 (VCAM1).
Further analyses to identify early predictors of Parkinson’s disease showed that higher ITGAV levels had the strongest association with increased disease risk in the model, with a 20% higher risk per 0.1-unit increase. In addition, changes in VCAM1 and CXCL12 – a molecule involved in attracting immune cells – were associated with about a 10%-15% increase in predicted risk.
Key protein network linked to inflammation and disease risk
CXCL12 signaling is known to activate pathways involved in the movement of microglia, the brain’s resident immune cells, and alpha-synuclein-related neuroinflammation, while ITGAV and VCAM1 help regulate immune cell adhesion and movement across blood vessels.
“We highlight pre-diagnosis molecular changes in the CXCL12 – cell adhesion molecules – integrin axis,” the researchers wrote, adding that “dysregulation of this axis could amplify [immune cell movement] and inflammatory cascades, supporting a model in which neurovascular immune interactions shift years before clinical onset.”
“Several proteins from this axis were reported individually in prior studies; here, we demonstrate that they form a coherent functional network that begins to change years before the clinical manifestation of PD,” the team wrote.
Benoit Lehallier, PhD, principal investigator of Chronos and senior director of data science at Alkahest, said: “Chronos reframes early disease detection by shifting from symptom-based evaluation to molecular trajectory profiling, offering a powerful foundation for accelerating the development of early detection and intervention tools at population scale.”
