Lower levels of uric acid and striatal dopamine in non-tremor dominant Parkinson's disease subtype

PLoS One. 2017 Mar 30;12(3):e0174644. doi: 10.1371/journal.pone.0174644. eCollection 2017.

Abstract

Parkinson's disease (PD) patients who present with tremor and maintain a predominance of tremor have a better prognosis. Similarly, PD patients with high levels of uric acid (UA), a natural neuroprotectant, have also a better disease course. Our aim was to investigate whether PD motor subtypes differ in their levels of UA, and if these differences correlate with the degree of dopamine transporter (DAT) availability. We included 75 PD patients from whom we collected information about their motor symptoms, DAT imaging and UA concentration levels. Based on the predominance of their motor symptoms, patients were classified into postural instability and gait disorder (PIGD, n = 36), intermediate (I, n = 22), and tremor-dominant (TD, n = 17) subtypes. The levels of UA and striatal DAT were compared across subtypes and the correlation between these two measures was also explored. We found that PIGD patients had lower levels of UA (3.7 vs 4.5 vs 5.3 mg/dL; P<0.001) and striatal DAT than patients with an intermediate or TD phenotype. Furthermore, UA levels significantly correlated with the levels of striatal DAT. We also observed that some PIGD (25%) and I (45%) patients had a predominance of tremor at disease onset. We speculate that UA might be involved in the maintenance of the less damaging TD phenotype and thus also in the conversion from TD to PIGD. Low levels of this natural antioxidant could lead to a major neuronal damage and therefore influence the conversion to a more severe motor phenotype.

MeSH terms

  • Adult
  • Corpus Striatum / diagnostic imaging
  • Corpus Striatum / metabolism
  • Dopamine / metabolism
  • Dopamine Plasma Membrane Transport Proteins / genetics
  • Dopamine Plasma Membrane Transport Proteins / isolation & purification*
  • Female
  • Gait / genetics*
  • Gait / physiology
  • Humans
  • Male
  • Middle Aged
  • Molecular Imaging / methods
  • Neuropsychological Tests
  • Parkinson Disease / blood*
  • Parkinson Disease / diagnostic imaging
  • Parkinson Disease / physiopathology
  • Postural Balance / genetics
  • Postural Balance / physiology
  • Uric Acid / blood*

Substances

  • Dopamine Plasma Membrane Transport Proteins
  • Uric Acid
  • Dopamine

Grants and funding

This work was supported by grants from the Instituto de Salud Carlos III [PI14/01823, PI16/01575], the Consejería de Economía, Innovación, Ciencia y Empleo de la Junta de Andalucía [CVI-02526, CTS-7685], the Consejería de Salud y Bienestar Social de la Junta de Andalucía [PI-0437-2012, PI-0471/2013], the Sociedad Andaluza de Neurología, the Jacques and Gloria Gossweiler Foundation, the Fundación Alicia Koplowitz and the Fundación Mutua Madrileña. Ismael Huertas was supported by the "PFIS" programme [FI14/00497], Silvia Jesús by the "Rio Hortega" programme, Juan Francisco Martin Rodríguez by the "Sara Borrell" programme, and Pilar Gómez-Garre by the "Miguel Servet" programme, all from the Instituto de Salud Carlos III.