SIRT2 Protein May Be Blood Marker of Parkinson’s That Differs from Atypical Parkinsonian Syndromes, Study Says

High levels of a protein called SIRT2 in the blood may serve as a diagnostic biomarker to differentiate between Parkinson’s patients and those with atypical Parkinson syndromes, a study finds.

Levels of this marker also may aid in diagnosing Parkinson’s at early stages.

The study, “Elevated Serum SIRT 2 May Differentiate Parkinson’s Disease From Atypical Parkinsonian Syndromes,” was published in the journal Frontiers in Molecular Science.

Patients with Parkinson’s typically show toxic clumps of the alpha-synuclein protein in the brain, which is thought to play a significant role in the disease’s development and progression.

Previous studies have shown an association between alpha-synuclein and a protein called SIRT2 in the context of Parkinson’s. In particular, SIRT2 seems to promote neurodegeneration by helping the buildup of alpha-synuclein plaques.

Atypical Parkinson syndromes are very similar to Parkinson’s and often have overlapping symptoms, including tremor, muscle stiffness and balance problems. These similarities make it hard to distinguish between the two, particularly early in the disease course.

A significant need for laboratory tests that can help doctors differentiate between these two exists. One strategy often used for diagnostic purposes and that can help differentiate in cases of similar diseases is looking at differences in the level of protein expression.

As SIRT2 is known to play a role in Parkinson’s, researchers studied whether levels of SIRT2 protein expression in the serum (a blood component) of Parkinson’s patients were different from those with atypical Parkinson syndromes and healthy elderly people serving as controls.

Serum SIRT2 protein levels were analyzed in 68 Parkinson’s patients, 34 people with atypical Parkinson syndromes, and 68 elderly controls. SIRT2 expression was correlated with alpha-synuclein levels in Parkinson’s and elderly controls.

Results showed SIRT2 expressed at significantly higher levels in people with Parkinson’s compared to those with atypical Parkinson syndromes or elderly controls. Importantly, SIRT2 levels could differentiate between Parkinson’s and atypical Parkinson syndromes patients with good sensitivity and specificity, as well as between people with atypical Parkinson syndromes and elderly controls.

In people with early stage Parkinson’s, a significant positive link was also seen between SIRT2 levels and a higher score on the Unified Parkinson’s Disease Rating Scale (UPDRS) part III motor score (which measures disease progression), the Hoehn & Yahr stage (which also measures disease activity and progression), and disease duration. In other words, higher SIRT2 levels correlate with disease activity and disease duration.

For the entire group of Parkinson’s patients evaluated, the link between SIRT2 levels and high UPDRS and Hoehn & Yahr scores did not hold.

This early stage finding is important because most Parkinson’s disease (PD) patients “are diagnosed at a late stage when vulnerable dopaminergic neurons in the substantia nigra [a midbrain area important to movement] have already been lost, and it is nearly impossible to detect PD by any screening test before the appearance of motor symptoms,” the researchers wrote.

“The present study is the first to report elevated serum SIRT2 in PD. The study also provided a simple test to distinguish PD from APS [atypical Parkinson syndromes] and may have translational utility for diagnosis,” they concluded.