Alpha-synuclein Blood Levels May Be Biomarker for Parkinson’s with Motor Symptoms

Measuring the levels of alpha-synuclein in red blood cells can reliably distinguish people with Parkinson’s disease and evident motor symptoms from healthy individuals, and could serve as a diagnostic biomarker, a study reports.

These levels in Parkinson’s patients with symptoms of dementia, however, did not measurably differ from healthy people serving as a control group.

The study, “α‐Synuclein in blood cells differentiates Parkinson’s disease from healthy controls,” was published in the journal Annals of Clinical and Translational Neurology.

The hallmark of Parkinson’s disease is the build-up of the protein alpha-synuclein in the brain, which goes on to form clumps of misfolded proteins known as Lewy bodies that damage nerve cells. 

Alpha-synuclein levels in the blood have been evaluated as a biomarker for Parkinson’s, as the ease and accessibility of a blood test would help with treatment during the course of the disease.

Low levels of misfolded alpha-synuclein — originating in neurons — have been found in the blood of Parkinson’s patients and are associated with disease progression.  

However, the primary source of alpha-synuclein in the blood comes from red blood cells, and little is known about the relevance of this source of alpha-synuclein and disease pathology.

To determine if alpha-synuclein levels in blood cells could be a biomarker for Parkinson’s, researchers at The Hebrew University‐Hadassah Medical School in Jerusalem tested the levels of alpha-synuclein in red blood cells isolated from 46 people with Parkinson’s. They compared them to those from 45 healthy controls. 

These blood samples were obtained from The BioFIND Study, an observational clinical study designed to discover and confirm Parkinson’s biomarkers. 

The overall levels of blood cells’ alpha-synuclein and misfolded alpha-synuclein were determined, as were known markers of Parkinson’s: phosphorylated and oxidized forms of alpha-synuclein. 

Alpha-synuclein phosphorylation — a chemical modification in which a phosphate group is added to the protein — and oxidation — which modifies the protein’s side chains —  are known to occur in Parkinson’s disease, and are thought to be critical steps in disease progression. They enhance alpha-synuclein’s toxicity, possibly by increasing the formation of alpha-synuclein aggregates (clumps).

Parkinson’s patients were divided into two groups: 32 people with motor symptoms and 14 with symptoms of dementia as determined by the Montreal Cognitive Assessment. Blood cell alpha-synuclein levels of these two groups were then compared to healthy controls. 

While the average levels of blood cell alpha-synuclein from both Parkinson’s groups combined were slightly lower than those of controls, alpha-synuclein levels in patients with motor symptoms were significantly higher than both controls and patients with dementia symptoms.

The levels of misfolded alpha-synuclein, in addition to its phosphorylated form, followed the same pattern — both were significantly higher in motor symptom patients and were found to correlate with disease severity. 

The test for oxidized alpha-synuclein found no differences between groups.

To validate these three tests as potential Parkinson’s biomarkers, the team collected a second set of blood samples from the Hadassah hospital, comprising 35 Parkinson’s patients with motor symptoms and 28 healthy controls. The levels of total, misfolded, and phosphorylated alpha-synuclein were measured.

This analysis confirmed that these three markers were able to reliably distinguish between Parkinson’s patients with motor symptoms and those without the disease. 

“We conclude that blood cells expressed [alpha-synuclein] can differentiate [Parkinson’s with motor symptoms] and [healthy controls] with a high degree of accuracy. It provides a reliable classification rate, correlates with the severity of disease and is reproducible,” the researchers wrote.

“A longitudinal study that will determine whether alterations in blood cell-expressed [alpha-synuclein] forms are associated with disease progression is required,” they added.