Effect of Tween-20 on Core Biomarkers Measured in Cerebrospinal Fluid from Patients with Alzheimer's Disease, Mild Cognitive Impairment, or Healthy Control Individuals

Background: There is substantial variation caused by preanalytical procedures in the measurement of cerebrospinal fluid (CSF) biomarkers for Alzheimer's disease (AD) reported in the literature. Objective: Determine whether the detergent Tween-20 improves diagnostic accuracy. Methods: CSF proteins (A beta(42), A beta(40), total tau, and phosphorylated tau) were measured by standard ELISA, in uncentrifuged CSF with or without 0.05% Tween-20 from patients with AD or amnestic mild cognitive impairment, and healthy elderly controls. In the main study, collection tubes containing Tween-20 (Sarstedt 15 mL) were filled with 5mL CSF to ensure consistent detergent concentration across subsequent aliquots into Corning 2mL tubes. These latter were also the primary collection vessel for samples without Tween-20. The effect of centrifugation, and extra tube transfer of samples with Tween-20 were also examined. Results: 0.05% Tween-20 significantly increased mean measured CSF concentration of A beta(42) (30%), A beta(40) (23%), and total tau (4%), but not phosphorylated tau. Generally, these increases were similar in all groups, although for A beta(42), the mean percentage increase with Tween-20 was slightly larger for AD. Areas under receiver-operator characteristic curves were similar whether Tween-20 was present or not. Centrifuged CSF without Tween-20 significantly reduced the measured concentration of A beta(42) versus non-centrifuged samples, a difference not seen when detergent was added. Similar CSF A beta(42) levels were found whether Tween-20 was added at collection in an extra tube or directly to the main collection tube. Conclusion: Addition of Tween-20 to CSF did not improve differentiation of patients from controls.