Extracellular α-synuclein is important in the pathogenesis of Parkinson disease (PD) and also as a potential biomarker when tested in the cerebrospinal fluid (CSF). The performance of blood plasma or serum α-synuclein as a biomarker has been found to be inconsistent and generally ineffective, largely due to the contribution of peripherally derived α-synuclein. In this study, we discovered, via an intracerebroventricular injection of radiolabeled α-synuclein into mouse brain, that CSF α-synuclein was readily transported to blood, with a small portion being contained in exosomes that are relatively specific to the central nervous system (CNS). Consequently, we developed a technique to evaluate the levels of α-synuclein in these exosomes in individual plasma samples. When applied to a large cohort of clinical samples (267 PD, 215 controls), we found that in contrast to CSF α-synuclein concentrations, which are consistently reported to be lower in PD patients compared to controls, the levels of plasma exosomal α-synuclein were substantially higher in PD patients, suggesting an increased efflux of the protein to the peripheral blood of these patients. Furthermore, although no association was observed between plasma exosomal and CSF α-synuclein, a significant correlation between plasma exosomal α-synuclein and disease severity (r=0.176, p=0.004) was observed, and the diagnostic sensitivity and specificity achieved by plasma exosomal α-synuclein were comparable to those determined by CSF α-synuclein. Further studies are clearly needed to elucidate the mechanism involved in the transport of CNS α-synuclein to the periphery, which may lead to a more convenient and robust assessment of PD clinically.

Background There is a clear need to develop biomarkers for Parkinson disease (PD) diagnosis, differential diagnosis of parkinsonian disorders, and monitoring disease progression. We and others have demonstrated that a decrease in DJ-1 and/or α-synuclein in the cerebrospinal fluid (CSF) is a potential index for PD diagnosis, but not for PD severity. Methods Using highly sensitive and quantitative Luminex assays, we measured total tau, phosphorylated tau, amyloid beta peptide 1-42 (Aβ1-42), Flt3 ligand and fractalkine levels in CSF in a large cohort of PD patients at different stages as well as healthy and diseased controls. The utility of these five markers was evaluated for disease diagnosis and severity/progression correlation alone, as well as in combination with DJ-1 and α-synuclein. The major results were further validated in an independent cohort of cross-sectional PD patients as well as in PD cases with CSF samples collected longitudinally. Findings The results demonstrated that combinations of these biomarkers could differentiate PD patients not only from normal controls but also from patients with Alzheimer disease and multiple system atrophy. Particularly, with CSF Flt3 ligand, PD could be clearly differentiated from multiple system atrophy, a disease that overlaps with PD clinically, with excellent sensitivity (99%) and specificity (95%). In addition, we identified CSF fractalkine/Aβ1-42 that positively correlated with PD severity in cross-sectional samples as well as with PD progression in longitudinal samples. Interpretation We have demonstrated that this panel of seven CSF proteins could aid in PD diagnosis, differential diagnosis, and correlation with disease severity and progression.

For many years, the echocardiographic quantitative assessment of right ventricular (RV) function has been difficult owing to the complex RV anatomy. Identifying an accurate and reliable echocardiographic parameter for the functional assessment of the RV still remains a challenge. The review presents a summary of the most studied and presently used parameters of RV function, with their reported normal values, as well as advantages and limitations of use. Combinations of these parameters are used in daily clinical practice, each one offering only partial information about the status of the RV. Myocardial velocity and strain rate imaging have promising results in the assessment of RV function. There is hope that novel myocardial deformation parameters and three-dimensional echocardiography-derived parameters may add value to the examination of the RV, but validation studies are still needed.

Background-Pregnancy provides a unique model to study the adaptation of the heart in a physiological situation of transient load changes. The aim of this study was to assess the performance of the left ventricle (LV) in normal, uncomplicated pregnancies while considering the actual LV load and shape. Methods and Results-Serial echocardiographic examinations were performed in 51 women in each pregnancy trimester and 3 to 6 months after delivery. Data from 10 nulliparous, age-matched women were used as the control. Conventional parameters of LV function (ejection fraction) as well as myocardial deformation (strain) were interpreted, taking into consideration maternal hemodynamics and LV shape. Cardiac output increased during pregnancy because of a higher stroke volume in early pregnancy and a late increase in heart rate, whereas total vascular resistance decreased. Progressive development of eccentric hypertrophy was observed, which subsequently recovered postpartum. Sphericity index decreased from the first to the third trimester (1.92Ϯ0.17 versus 1.71Ϯ0.17) and returned postpartum to values comparable to the control. Although higher LV stroke work was noted toward the third trimester (5.9Ϯ1.1 versus 5.3Ϯ1.0 Newton meter, PϽ0.001), ejection fraction showed no significant changes. LV strain decreased significantly in late pregnancy (Ϫ19.5Ϯ2% to Ϫ17.6Ϯ1.6%, PϽ0.001) and returned to baseline values after delivery (Ϫ19.5Ϯ2%). Conclusions-Pregnancy is a physiological process associated with increased cardiac performance and progressive LV remodeling. These changes are not directly reflected by parameters traditionally considered to describe systolic function, such as ejection fraction and longitudinal deformation. While ejection fraction was insensitive to the functional changes, the transient decrease in longitudinal deformation becomes only plausible when considering the changes in LV geometry. (Circ Cardiovasc Imaging. 2012;5:289-297.)