Optimized Standard Operating Procedures for the Analysis of Cerebrospinal Fluid Aβ42 and the Ratios of Aβ Isoforms Using Low Protein Binding Tubes

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Vanderstichele, Hugo Marcel JohanADx NeuroSciences (author)

Optimized Standard Operating Procedures for the Analysis of Cerebrospinal Fluid Aβ42 and the Ratios of Aβ Isoforms Using Low Protein Binding Tubes

Article/chapterEnglish2016

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2016
12 s.

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LIBRIS-ID:oai:lup.lub.lu.se:fbd6f55f-eaf7-4c3e-9036-c7a6eebd9b84
https://lup.lub.lu.se/record/fbd6f55f-eaf7-4c3e-9036-c7a6eebd9b84URI
https://doi.org/10.3233/JAD-160286DOI

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Language:English
Summary in:English

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Background: Reduced cerebrospinal fluid (CSF) concentration of amyloid-β1-42 (Aβ1-42) reflects the presence of amyloidopathy in brains of subjects with Alzheimer's disease (AD). Objective: To qualify the use of Aβ1-42/Aβ1-40 for improvement of standard operating procedures (SOP) for measurement of CSF Aβ with a focus on CSF collection, storage, and analysis. Methods: Euroimmun ELISAs for CSF Aβ isoforms were used to set up a SOP with respect to recipient properties (low binding, polypropylene), volume of tubes, freeze/thaw cycles, addition of detergents (Triton X-100, Tween-20) in collection or storage tubes or during CSF analysis. Data were analyzed with linear repeated measures and mixed effects models. Results: Optimization of CSF analysis included a pre-wash of recipients (e.g., tubes, 96-well plates) before sample analysis. Using the Aβ1-42/Aβ1-40 ratio, in contrast to Aβ1-42, eliminated effects of tube type, additional freeze/thaw cycles, or effect of CSF volumes for polypropylene storage tubes. 'Low binding' tubes reduced the loss of Aβ when aliquoting CSF or in function of additional freeze/thaw cycles. Addition of detergent in CSF collection tubes resulted in an almost complete absence of variation in function of collection procedures, but affected the concentration of Aβ isoforms in the immunoassay. Conclusion: The ratio of Aβ1-42/Aβ1-40 is a more robust biomarker than Aβ1-42 toward (pre-) analytical interfering factors. Further, 'low binding' recipients and addition of detergent in collection tubes are able to remove effects of SOP-related confounding factors. Integration of the Aβ1-42/Aβ1-40 ratio and 'low-binding tubes' into guidance criteria may speed up worldwide standardization of CSF biomarker analysis.

Subject headings and genre

MEDICIN OCH HÄLSOVETENSKAP Klinisk medicin Neurologi hsv//swe
MEDICAL AND HEALTH SCIENCES Clinical Medicine Neurology hsv//eng
Amyloid
cerebrospinal fluid
ELISA
improvement
standard operating procedure

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Janelidze, ShorenaLund University,Lunds universitet,Klinisk minnesforskning,Forskargrupper vid Lunds universitet,Clinical Memory Research,Lund University Research Groups(Swepub:lu)nkir-sje (author)
Demeyer, LeentjeADx NeuroSciences (author)
Coart, ElsInternational Drug Development Institute (author)
Stoops, ErikADx NeuroSciences (author)
Herbst, VictorEuroimmun Medizinische Labordiagnostika AG (author)
Mauroo, KimberleyADx NeuroSciences (author)
Brix, Britta (author)
Hansson, OskarLund University,Lunds universitet,Klinisk minnesforskning,Forskargrupper vid Lunds universitet,Clinical Memory Research,Lund University Research Groups,Skåne University Hospital(Swepub:lu)mphy-ohn (author)
ADx NeuroSciencesKlinisk minnesforskning (creator_code:org_t)

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In:Journal of Alzheimer's Disease53:3, s. 1121-11321387-2877

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By the author/editor: Vanderstichele, ...; Janelidze, Shore ...; Demeyer, Leentje; Coart, Els; Stoops, Erik; Herbst, Victor; show more...; Mauroo, Kimberle ...; Brix, Britta; Hansson, Oskar; show less...

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MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Clinical Medicin ...; and Neurology

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