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

Article type: Research Article

Authors: Berge, Guro^a | Lauridsen, Camilla^a | Sando, Sigrid Botne^{a; b} | Holder, Daniel Joseph^c | Møller, Ina^b | Aasly, Jan Olav^{a; b} | Bråthen, Geir^{a; b} | Savage, Mary Josephine^c | White, Linda Rosemary^{a; b; *}

Affiliations: [a] Department of Neuroscience, Faculty of Medicine, Norwegian University of Science and Technology, Trondheim, Norway | [b] Department of Neurology, University Hospital of Trondheim, Norway | [c] Department of Molecular Biomarkers, Merck & Co., Inc., West Point, PA, USA

Correspondence: [*] Correspondence to: Linda R. White, PhD, Department of Neuroscience, Faculty of Medicine, Norwegian University of Science and Technology, NO-7030 Trondheim, Norway. Tel.: +47 72 57 51 57; Fax: +47 72 57 55 63; E-mail: [email protected]

Abstract: 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 (Aβ42, Aβ40, 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 5 mL CSF to ensure consistent detergent concentration across subsequent aliquots into Corning 2 mL 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 Aβ42 (30% ), Aβ40 (23% ), and total tau (4% ), but not phosphorylated tau. Generally, these increases were similar in all groups, although for Aβ42, 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 Aβ42 versus non-centrifuged samples, a difference not seen when detergent was added. Similar CSF Aβ42 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.

Keywords: Amyloid beta-peptides, dementia, human, synthetic detergent, tau protein

DOI: 10.3233/JAD-150234

Journal: Journal of Alzheimer's Disease, vol. 49, no. 2, pp. 493-502, 2016