No abstract

Background Phosphorylated tau (pTau), total tau (tTau), and β-amyloid (Aβ) are established cerebrospinal fluid (CSF) biomarkers used to help diagnose Alzheimer disease. Preanalytic workups of CSF samples lack harmonization, making interlaboratory comparison of these biomarkers challenging. The Aβ adsorbs to sample tubes, yielding underestimated concentrations, and may result in false Alzheimer disease diagnosis. Our primary aim was to compare Aβ recovery across multiple polypropylene tubes and to test the stability of tTau, pTau, and Aβ in the best performing tube. Methods Eight polypropylene tubes were tested using 3 CSF pools with Aβ concentrations <500, 500–1000, and >1000 ng/L. All samples were analyzed in duplicate. Tubes were cut open to assess their different infrared adsorption spectra. Freshly drawn CSF from 14 patients was distributed into 4 Sarstedt 5-mL (no. 63.504.027; Sar5CSF) tubes, left at room temperature for up to 7 days, and analyzed for pTau, tTau, and Aβ by ELISA. Results Two Sarstedt 5-mL tubes and a Sarstedt 10-mL (Sar10CSF) tube showed significantly higher Aβ recovery at all 3 concentrations compared with the 5 other tubes. The infrared adsorption spectra of Sar10CSF and Sar5CSF tubes were practically identical, unlike the other tubes. No significant loss of pTau, tTau, and Aβ was observed in CSF left at room temperature for up to 7 days (P > 0.05). Conclusions Recovery of Aβ from Sar5CSF tubes is equivalent to Aβ recovery from Sar10CSF tubes. Levels of pTau, tTau, and Aβ were stable for at least 7 days at room temperature but not at 37 °C.

Background Growth differentiation factor 15 (GDF-15) is upregulated in response to both acute and chronic cardiac injury, and concentrations of GDF-15 are increased in acute myocardial infarction and acute heart failure. Associations between GDF-15, left ventricular structure and preclinical stages of left ventricular dysfunction in the general population remain unclear. Methods We measured GDF-15 in 1237 women and 1158 men participating in the prospective observational Akershus Cardiac Examination (ACE) 1950 Study, which included community dwellers aged 63–65 residing in Akershus county, Norway. All study participants were free from known coronary heart disease and underwent extensive cardiovascular phenotyping at baseline, including detailed echocardiography. Regression models were constructed on global longitudinal strain (GLS), left ventricular mass index (LVMI), and left ventricular ejection fraction (LVEF), and adjusted for demographics, established cardiovascular risk factors, hs-cTnT and NT-proBNP. Results Concentrations of GDF-15 were measurable in 98.1% of study participants, and were positively associated with male sex, age, BMI, current smoking, diabetes mellitus, as well as concentrations C-reactive protein, hs-cTnT and NT-proBNP. Higher education, alcohol consumption, eGFR and concentrations of total cholesterol were all associated with lower concentrations of GDF-15. Concentrations of lnGDF-15 were significantly associated with GLS (B −0.44 [95% CI −0.70 to −0.18]; Figure) and LVEF (B 0.72 [95% CI 0.14–1.29]), but not LVMI (Table). Table 1. Associations between GDF-15 and indices of left ventricular structure and function. Model 1 Model 2 Model 3 B (95% CI)   GLS (n=2395) 0.17 (−0.07 to 0.42) −0.04 (−0.28 to 0.20) −0.44 (−0.70 to −0.18)   LVEF (n=2383) 0.01 (−0.52 to 0.54) 0.21 (−0.31 to 0.73) 0.72 (0.14 to 1.29)   LVMI (n=2371) 2.00 (0.32 to 3.68) −0.37 (−1.98 to 1.24) −0.42 (−2.16 to 1.33) OR (95% CI)   GLS (n=2395) 1.35 (0.98 to 1.87) 1.28 (0.92 to 1.78) 0.81 (0.56 to 1.17)   LVEF (n=2383) 1.04 (0.75 to 1.44) 0.88 (0.62 to 1.24) 0.73 (0.50 to 1.07)   LVMI (n=2371) 1.27 (0.91 to 1.76) 1.12 (0.79 to 1.57) 1.11 (0.75 to 1.64) Linear regression models constructed on continuous levels of GLS, LVMI and LVEF. Logistic regression models constructed on the upper sex specific deciles of GLS and LVMI, and on the lower sex specific decile of LVEF. GDF-15, hs-cTnT and NT-proBNP were all transformed by the natural logarithm. Model 1, unadjusted. Model 2, adjusted for sex, age and study site. Model 3, adjusted for sex, age, study site, BMI, eGFR, total and HDL cholesterol, CRP, higher education, hypertension, diabetes mellitus, statin use, current smoking, alcohol consumption, hs-cTnT and NT-proBNP. Figure 1 Conclusion Concentrations of GDF-15 are inversely associated with GLS, a highly sensitive index of subclinical myocardial dysfunction. In healthy subjects free from known cardiovascular disease, GDF-15 appears protective and promotes beneficial cardiac function.