Josef Pannee1, Johan Gobom2, Leslie M Shaw3, Magdalena Korecka3, Erin E Chambers4, Mary Lame4, Rand Jenkins5, William Mylott5, Maria C Carrillo6, Ingrid Zegers7, Henrik Zetterberg8, Kaj Blennow2, Erik Portelius2. 1. Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Salgrenska Academy, University of Gothenburg, Mölndal, Sweden. Electronic address: josef.pannee@neuro.gu.se. 2. Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Salgrenska Academy, University of Gothenburg, Mölndal, Sweden. 3. Department of Pathology & Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. 4. Waters Corporation, Milford, MA, USA. 5. Chromatographic Sciences Department, PPD Laboratories, Richmond, VA, USA. 6. Medical & Scientific Relations Division, Alzheimer's Association, Chicago, IL, USA. 7. Institute for Reference Materials and Measurements (IRMM), Joint Research Centre, European Commission, Geel, Belgium. 8. Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Salgrenska Academy, University of Gothenburg, Mölndal, Sweden; UCL Institute of Neurology, London, UK.
Abstract
INTRODUCTION: Cerebrospinal fluid (CSF) amyloid-β 1-42 (Aβ42) is an important biomarker for Alzheimer's disease, both in diagnostics and to monitor disease-modifying therapies. However, there is a great need for standardization of methods used for quantification. To overcome problems associated with immunoassays, liquid chromatography-tandem mass spectrometry (LC-MS/MS) has emerged as a critical orthogonal alternative. METHODS: We compared results for CSF Aβ42 quantification in a round robin study performed in four laboratories using similar sample preparation methods and LC-MS instrumentation. RESULTS: The LC-MS results showed excellent correlation between laboratories (r(2) >0.98), high analytical precision, and good correlation with enzyme-linked immunosorbent assay (r(2) >0.85). The use of a common reference sample further decreased interlaboratory variation. DISCUSSION: Our results indicate that LC-MS is suitable for absolute quantification of Aβ42 in CSF and highlight the importance of developing a certified reference material.
INTRODUCTION: Cerebrospinal fluid (CSF) amyloid-β 1-42 (Aβ42) is an important biomarker for Alzheimer's disease, both in diagnostics and to monitor disease-modifying therapies. However, there is a great need for standardization of methods used for quantification. To overcome problems associated with immunoassays, liquid chromatography-tandem mass spectrometry (LC-MS/MS) has emerged as a critical orthogonal alternative. METHODS: We compared results for CSF Aβ42 quantification in a round robin study performed in four laboratories using similar sample preparation methods and LC-MS instrumentation. RESULTS: The LC-MS results showed excellent correlation between laboratories (r(2) >0.98), high analytical precision, and good correlation with enzyme-linked immunosorbent assay (r(2) >0.85). The use of a common reference sample further decreased interlaboratory variation. DISCUSSION: Our results indicate that LC-MS is suitable for absolute quantification of Aβ42 in CSF and highlight the importance of developing a certified reference material.
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