Elevated Serum SIRT 2 May Differentiate Parkinson's Disease From Atypical Parkinsonian Syndromes

Atypical Parkinson syndromes (APSs) often have symptoms that overlap with those of Parkinson's disease (PD), especially early in the disease, making these disorders difficult to diagnose. Previous studies have demonstrated an association of oligomeric alpha-synuclein (alpha-Syn), a key element in the pathogenesis of PD, with Sirtuin (SIRT)2 proteins for modulating PD. We aimed to evaluate SIRT protein expression in serum of PD patients and compare it with APSs and normal elderly control (GC) and to correlate this with alpha-Syn. SIRT protein expression was evaluated in sera of 68 PD; 34 APS and 68 GC without any neuro-psychiatric illness as controls by surface plasmon resonance (SPR). SIRT2 expression was correlated with alpha-Syn in PD and GC. Significant (p < 0.0001) differences were observed between serum SIRT2 concentration in PD and APS and GC as well as between APS and GC. Receiver operating characteristic (ROC) analysis revealed the strong cut-off value to differentiate PD from APS and GC and also APS from GC. Significant correlation was observed among SIRT2 levels in early PD patients with Unified Parkinson's Disease Rating Scale (UPDRS), Hoehn & Yahr (H & Y) and increased duration of disease. In addition, a strong positive correlation of SIRT2 with alpha-Syn (p < 0.0001) was observed. However, no such difference was detected for serum SIRT1 in cases of PD and APS or for GC. 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 and may have translational utility for diagnosis.