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 (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.


CONCLUSIONS
Addition of Tween-20 to CSF did not improve differentiation of patients from controls.
Department of Neuroscience, Faculty of Medicine, Norwegian University of Science and Technology, Trondheim, Norway.
Guro
G
Berge
Department of Neuroscience, Faculty of Medicine, Norwegian University of Science and Technology, Trondheim, Norway.
Camilla
C
Lauridsen
Department of Neuroscience, Faculty of Medicine, Norwegian University of Science and Technology, Trondheim, Norway.|Department of Neurology, University Hospital of Trondheim, Norway.
Sigrid Botne
SB
Sando
Department of Molecular Biomarkers, Merck & Co., Inc., West Point, PA, USA.
Daniel Joseph
DJ
Holder
Department of Neurology, University Hospital of Trondheim, Norway.
Ina
I
Møller
Department of Neuroscience, Faculty of Medicine, Norwegian University of Science and Technology, Trondheim, Norway.|Department of Neurology, University Hospital of Trondheim, Norway.
Jan Olav
JO
Aasly
Department of Neuroscience, Faculty of Medicine, Norwegian University of Science and Technology, Trondheim, Norway.|Department of Neurology, University Hospital of Trondheim, Norway.
Geir
G
Bråthen
Department of Molecular Biomarkers, Merck & Co., Inc., West Point, PA, USA.
Mary Josephine
MJ
Savage
Department of Neuroscience, Faculty of Medicine, Norwegian University of Science and Technology, Trondheim, Norway.|Department of Neurology, University Hospital of Trondheim, Norway.
Linda Rosemary
LR
White
D000368:Aged; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid*; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid / Q000187:drug effects*; D060825:Cognitive Dysfunction / Q000134:cerebrospinal fluid*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000134:cerebrospinal fluid / Q000187:drug effects*; D010766:Phosphorylation / Q000187:drug effects; D011136:Polysorbates / Q000494:pharmacology*; D012372:ROC Curve; D013501:Surface-Active Agents / Q000494:pharmacology*; D016875:tau Proteins / Q000134:cerebrospinal fluid / Q000187:drug effects*
D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; D011136:Polysorbates; D013501:Surface-Active Agents; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42); D016875:tau Proteins
Amyloid beta-peptides; dementia; human; synthetic detergent; tau protein