Reduction in presynaptic dopamine transporter may be associated with future problematic delusion.

OBJECTIVES: Psychosis, especially in delusions, greatly impairs the quality of life of patients with Parkinson's disease (PD) and their caregivers. Few objective risk indicators of the association between psychosis and clinical features has been reported. It is unclear whether the reduction in DAT binding represents the underlying mechanism of delusion or its association. There are no long-term data on the objective prognostic value of DAT binding for delusions. We investigated whether DAT binding at baseline can be a prognostic risk factor for future development of PD delusions. MATERIALS AND METHODS: We reviewed the detailed clinical chart of patients with PD without a history of psychosis who underwent [123I]FP-CIT SPECT during the disease. The endpoint was defined as when the delusions occurred during the 5 years after the examination of [123I]FP-CIT SPECT. Specific binding ratio (SBR) values were calculated. RESULTS: Sixty-one patients with PD were included in the analysis, and 11 patients had delusions within 5 years of [123I] FP-CIT SPECT. The average (p = 0.004), minimum (p = 0.004), maximum (p = 0.001), right-sided (p = 0.002), and left-sided (p = 0.003) SBRs in the striatum were significantly smaller in patients with delusions than in patients without delusions. Each difference of each SBR was significantly smaller than those without delusions after adjusting after controlling for age, gender, disease severity, timing of [123I]FP-CIT SPECT, anti-parkinsonian medications, hospitalization, administering more or newly anti-parkinsonian drugs, and receiving DBS or LCIG. CONCLUSIONS: PD delusions is still problematic, and lowering DAT binding may be helpful for predicting future delusions, regardless of the timing of [123I]FP-CIT SPECT.

Identification of three distinct cell populations for urate excretion in human kidneys.

In humans, uric acid is an end-product of purine metabolism. Urate excretion from the human kidney is tightly regulated by reabsorption and secretion. At least eleven genes have been identified as human renal urate transporters. However, it remains unclear whether all renal tubular cells express the same set of urate transporters. Here, we show renal tubular cells are divided into three distinct cell populations for urate handling. Analysis of healthy human kidneys at single-cell resolution revealed that not all tubular cells expressed the same set of urate transporters. Only 32% of tubular cells were related to both reabsorption and secretion, while the remaining tubular cells were related to either reabsorption or secretion at 5% and 63%, respectively. These results provide physiological insight into the molecular function of the transporters and renal urate handling on single-cell units. Our findings suggest that three different cell populations cooperate to regulate urate excretion from the human kidney, and our proposed framework is a step forward in broadening the view from the molecular to the cellular level of transport capacity.