Blood Levels of SIRT1 Protein May Mark Parkinson’s and Its Severity

Lower-than-usual levels of the protein SIRT1 are evident in the blood of people with Parkinson’s disease, and correlate with greater disease severity and cognitive impairment, a study reported.

A blood test of SIRT1 levels, for this reason, may serve as a biomarker in diagnosing the disease and in monitoring its progression. 

The study, “Reduced serum SIRT1 levels in patients with Parkinson’s disease: a cross-sectional study in China,” was published in the journal Neurological Sciences. 

Parkinson’s disease is difficult to diagnose, as there is no definitive test. Diagnosis mainly depends on the appearance of symptoms, which can overlap with those of other neurodegenerative diseases and are also associated with aging.

A need exists for validated biomarkers — measurable indicators of disease — that  help in detecting Parkinson’s and tracking its progression. 

Different studies have identified a link between a protein called Sirtuin 1 (SIRT1) and Parkinson’s progression. SIRT1 was found to promote the survival of dopaminergic neurons — nerve cells that produce the signaling molecule dopamine and that are damaged in people with this disease.

Researchers at the Nantong University in China designed a study to determine whether SIRT1 could be used as a biomarker for Parkinson’s by measuring its levels in the liquid portion of blood known as the serum. 

“Given that few reports evaluated serum SIRT1 levels in [Parkinson’s disease] patients, we aimed to investigate this in our study to assess its value as a potential biomarker” of this disease, the researchers wrote.

Blood samples were collected from 31 men and 27 women with Parkinson’s (mean age, 69.5) and 91 age- and gender-matched healthy participants serving as controls. 

The median (middle) level of serum SIRT1 in Parkinson’s patients was 0.37 nanograms (ng) /mL, which was significantly lower than controls at 0.55 ng/mL. 

The analysis’s sensitivity was 71%, which reflected the test’s ability to identify those with the disease correctly. The specificity was 71%, which indicates the test’s validity to identify those without the disease. The diagnostic cut-off value was found to be 0.47 ng/mL, meaning a level below this value was an indicator of Parkinson’s. 

Higher serum SIRT1 levels correlated with a later age of disease onset and higher scores on the Mini-Mental State Examination (MMSE), a measure of cognitive impairment in which higher scores reflect healthy cognition. 

In contrast, a lower serum SIRT1 level correlated with longer disease duration and a higher stage of progression as measured by the Hoehn and Yahr staging scale (H-Y) and the Unified Parkinson’s Disease Rating Scale (UPDRS-III). 

Patients at a higher H-Y stage of disease progression had significantly lower serum SIRT1 (0.26 ng/mL) compared with those at early stages (0.41 ng/mL).

Based on the MMSE scores, patients with and without cognitive impairment were compared. Those with impairment had a longer disease duration, more advanced H-Y stage, higher UPDRS III stage, and lower SIRT1 levels (0.25 ng/mL) than did patients without cognitive impairment (0.41 ng/mL). 

After adjusting for age, gender, disease duration, H-Y stage, UPDRS III stage, and levodopa dosage equivalents (contribution made by each Parkinson’s medication), the significant relationship between SIRT1 and cognitive impairment remained.

Here, the SIRT1 test for Parkinson’s-related cognitive impairment had a sensitivity of 67%, a 77% specificity, and a cut-off value of 0.27 ng/ml. 

“In conclusion, we firstly report that serum SIRT1 was decreased in [Parkinson’s disease] patients,” the researchers wrote. “Besides, it was correlated with disease severity and cognitive function.”

Further studies, they added, “are needed to verify the clinical diagnostic value of serum SIRT1 in [Parkinson’s disease] and to extensively explore its underlying molecular mechanisms in the future.”