Parkinson's disease, the most common age-related movement disorder, is a progressive neurodegenerative disease with unclear etiology. Better understanding of the underlying disease mechanism(s) is an urgent need for the development of disease-modifying therapeutics. Limited studies have been performed in large patient cohorts to identify protein alterations in cerebrospinal fluid (CSF), a proximal site to pathology. We set out to identify disease-relevant protein changes in CSF to gain insights into the etiology of Parkinson's disease and potentially assist in disease biomarker identification. In this study, we used liquid chromatography-tandem mass spectrometry in dataindependent acquisition (DIA) mode to identify Parkinson's-relevant biomarkers in cerebrospinal fluid. We quantified 341 protein groups in two independent cohorts (n = 196) and a longitudinal cohort (n = 105 samples, representing 40 patients) consisting of Parkinson's disease and healthy control samples from three different sources. A first cohort of 53 Parkinson's disease and 72 control samples was analyzed, identifying 53 proteins with significant changes (p < 0.05) in Parkinson's disease relative to healthy control. We established a biomarker signature and multiple protein ratios that differentiate Parkinson's disease from healthy controls and validated these results in an independent cohort. The second cohort included 28 Parkinson's disease and 43 control samples. Independent analysis of these samples identified 41 proteins with significant changes. Evaluation of the overlapping changes between the two cohorts identified 13 proteins with consistent and significant changes (p < 0.05). Importantly, we found the extended granin family proteins as reduced in disease, suggesting a potential common mechanism for the biological reduction in monoamine neurotransmission in Parkinson's patients. Our study identifies several novel protein changes in Parkinson's disease cerebrospinal fluid that may be exploited for understanding etiology of disease and for biomarker development.

Background Adenosine A2A receptor antagonists reduce or prevent the development of dyskinesia in animal models of levodopa-induced dyskinesia. Methods We examined the association between self-reported intake of the A2A receptor antagonist caffeine and time to dyskinesia in the Comparison of the Agonist Pramipexole with Levodopa on Motor Complications of Parkinson’s Disease (CALM-PD) and CALM Cohort extension studies, using a Cox proportional hazards model adjusting for age, baseline Parkinson’s severity, site, and initial treatment with pramipexole or levodopa. Results For subjects who consumed > 12 ounces of coffee/day, the adjusted hazard ratio for the development of dyskinesia was 0.61 (95% confidence interval, 0.37–1.01) compared to subjects who consumed < 4 ounces/day. For subjects who consumed between 4 and 12 ounces/day, the adjusted hazard ratio was 0.73 (C.I. 0.46–1.15) (test for trend, p = 0.05). Conclusions These results support the possibility that caffeine may reduce the likelihood of developing dyskinesia.

Background: In the current study, we aimed to determine normative values for muscle thickness and fasciculation prevalence in healthy subjects.Methods: We performed a prospective study from October to December 2018 in 65 healthy subjects. All subjects underwent quantitative sonographic evaluation of muscle thickness and fasciculation prevalence in the following 8 muscles: Biceps brachii, abductor pollicis brevis, first dorsal interosseous, abductor digiti minimi, quadriceps, tibialis anterior, extensor digitorum brevis, and abductor hallucis brevis.Results: Subject ages ranged from 21 to 82 years, with 63% women. Normative values for muscle thickness were determined using the fifth percentile. Multivariate regression analysis showed that sex, age, body mass index, and hand dominance affected muscle thickness. Fasciculations were observed frequently only in distal muscles.Conclusions: Normal values for muscle thickness were determined, and may enhance neuromuscular ultrasound sensitivity and serve as a basis for future studies. Larger series are needed to confirm these values.fasciculations, muscle thickness, muscle ultrasound, neuromuscular disorders, neuromuscular ultrasound, normative values