Serum Tyrosine-to-Phenylalanine Ratio is Low in Parkinson's Disease

Noninvasive biomarkers for Parkinson's disease (PD) are currently unavailable.

To search for a biomarker unique to PD in sweat and serum.

Sweat samples in 42 PD patients and 16 controls were analyzed using liquid chromatography/mass spectrometry (LC/MS). The principal component analysis (PCA) and the orthogonal projections to latent structures (OPLS) analysis were employed. Serum Phe and Tyr levels were determined using the HPLC-fluorescence detection system in 28 de novo PD patients, 52 L-Dopa-treated PD patients, and 27 controls.

PCA and OPLS analyses of LC/MS of sweat samples revealed that Tyr, Phe, Leu (Ile), and Asp have high effect sizes to differentiate PD and controls. As Phe and Tyr are precursors of dopamine, we quantified the serum Phe and Tyr levels in de novo and treated PD patients, as well as in controls. Phe was high in de novo patients, but not in treated patients. In contrast, Tyr tended to be low in treated patients, but not in de novo patients. Tyr/Phe ratios were lower in both de novo and treated patients than in controls. The Tyr/Phe ratios were all higher than 0.82 in controls, whereas 49% of the de novo and treated patients had Tyr/Phe ratios less than 0.82. The low Tyr/Phe ratios were associated with male patients and low doses of entacapone. However, Tyr/Phe ratios were not different between male and female patients, and between patients with and without entacapone.

The low serum Tyr/Phe ratio differentiates PD from controls with sensitivity = 0.49, specificity = 1.00, positive predictive value = 1.00, and negative predictive value = 0.40.