P1–170: Evaluation of pre‐analytical and analytical factors that contribute to variability in CSF biomarker levels
Year: 2013
Type: article
Abstract: Studies of CSF from Alzheimer's disease research cohorts have identified several markers of disease pathology which show utility for disease diagnosis and prognosis (even in early and pre-clinical stages). However, anecdotal observations, lab-specific experiments and more recently, a world-wide initiative have shed light on the adverse influence of various pre-analytical, analytical and post-analytical factors on CSF biomarker values. Development of disease-modifying therapies and the proposed revision of diagnostic criteria that include biomarkers make biomarker protocol optimization and standardization a top priority. To promote such efforts, we have evaluated several potential sources of methodological variability in analyses of CSF. Existing CSF samples obtained from well-characterized research volunteers at the Knight Alzheimer's Disease Research Center were analyzed by plate-based ELISA or bead-based immunoassays for A b 40, A b 42, tau and/or ptau181. Investigated potential sources of variability included: assay platform type, commercial kit lot number, two vendor-specific polypropylene aliquot tubes, use of sample pre-plate during analysis, aliquot volume, number of wells used to generate a mean value, and inter-personnel performance. Student's t tests and Pearson correlation coefficients were used to evaluate data correspondence. Analyte values did not differ between the two polypropylene aliquot tube types evaluated, whereas aliquot size did have an effect. Assay platform had a large impact on absolute analyte values, although values obtained between platforms were highly correlated. Commercial kit lot-to-lot variability was observed to varying extents and, when present, had a substantial impact on the evaluation of longitudinal biomarker changes within individuals over time. Mean values generated from samples run in duplicate were as precise as those run in quadruplicate for the assay tested. Use of a pre-plate for sample loading influenced levels of A b 42 but not levels of tau or ptau181. High inter-personnel reliability was achieved when well-trained individuals used identical protocols. Several sources of pre-analytical and analytical variability in the measurement of CSF biomarkers exist, and thus could impact the diagnostic and prognostic utility of such markers. Protocol standardization efforts within laboratories and eventually between laboratories are needed in order to increase the usefulness of these markers in both the research and clinical settings.
Source: Alzheimer s & Dementia
Institution: Washington University in St. Louis
Language: English
Subfield: Physiology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W2053637874