Pre-analytical protocol for measuring Alzheimer's disease biomarkers in fresh CSF.

INTRODUCTION: We aimed to establish a standardized, routine-use pre-analytical protocol for measuring Alzheimer's disease (AD) biomarkers in cerebrospinal fluid (CSF). METHODS: The effect of pre-analytical factors (sample collection/handling/storage/transportation) on biomarker levels was assessed using freshly collected CSF. Tube type/sterilization was assessed using previously frozen samples. A low-bind false-bottom tube (FBT, Sarstedt) was used for all experiments, except tube types/sterilization experiments. Biomarkers were measured using Elecsys CSF assays. RESULTS: Amyloid beta (Aß)1-42 levels varied by tube type, using a low-bind FBT reduced variation. Aß1-42 levels were higher with no mixing versus roller/inversion mixing. Aß1-42 levels were lower with horizontal versus upright transportation; this was resolved by maximal tube filling and storage at 2°C to 8°C. Aß1-40 levels were less strongly affected. Phospho-tau and total-tau levels were largely unaffected. DISCUSSION: We propose an easy-to-use, standardized, routine-use pre-analytical protocol, using low-bind FBTs, for measuring AD CSF biomarkers in clinical practice.

Error Propagation in Isometric Log-ratio Coordinates for Compositional Data: Theoretical and Practical Considerations.

Compositional data, as they typically appear in geochemistry in terms of concentrations of chemical elements in soil samples, need to be expressed in log-ratio coordinates before applying the traditional statistical tools if the relative structure of the data is of primary interest. There are different possibilities for this purpose, like centered log-ratio coefficients, or isometric log-ratio coordinates. In both the approaches, geometric means of the compositional parts are involved, and it is unclear how measurement errors or detection limit problems affect their presentation in coordinates. This problem is investigated theoretically by making use of the theory of error propagation. Due to certain limitations of this approach, the effect of error propagation is also studied by means of simulations. This allows to provide recommendations for practitioners on the amount of error and on the expected distortion of the results, depending on the purpose of the analysis.