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Metrologically Traceable Quantification of 3 Apolipoprotein E Isoforms in Cerebrospinal Fluid.
Huynh, Huu-Hien; Kuch, Kellie; Orquillas, Allen; Forrest, Katrina; Barahona-Carrillo, Lili; Keene, Dirk; Henderson, Victor W; Wagner, Anthony D; Poston, Kathleen L; Montine, Thomas J; Lin, Amy; Tian, Lu; MacCoss, Michael J; Emrick, Michelle A; Hoofnagle, Andrew N.
Afiliación
  • Huynh HH; Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA, United States.
  • Kuch K; Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA, United States.
  • Orquillas A; Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA, United States.
  • Forrest K; Department of Epidemiology and Population Health, Stanford University, Stanford, CA, United States.
  • Barahona-Carrillo L; Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA, United States.
  • Keene D; Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA, United States.
  • Henderson VW; Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA, United States.
  • Wagner AD; Department of Epidemiology and Population Health, Stanford University, Stanford, CA, United States.
  • Poston KL; Department of Neurology and Neurological Science, Stanford University School of Medicine, Stanford, CA, United States.
  • Montine TJ; Department of Psychology, Stanford University, Stanford, CA, United States.
  • Lin A; Department of Neurology and Neurological Science, Stanford University School of Medicine, Stanford, CA, United States.
  • Tian L; Department of Pathology, Stanford University School of Medicine, Stanford, CA, United States.
  • MacCoss MJ; Department of Biomedical Data Science, Stanford University School of Medicine, Stanford, CA, United States.
  • Emrick MA; Department of Biomedical Data Science, Stanford University School of Medicine, Stanford, CA, United States.
  • Hoofnagle AN; Department of Genome Sciences, University of Washington, Seattle, WA, United States.
Clin Chem ; 69(7): 734-745, 2023 07 05.
Article en En | MEDLINE | ID: mdl-37279935
BACKGROUND: APOE genotype is associated with Alzheimer disease. Thus, the concentration of apolipoprotein E (apoE) isoforms in cerebrospinal fluid (CSF) could be altered in dementia. However, conflicting results have been obtained in different studies. Carefully validated and standardized assays could improve the interpretation of research findings, allow their replication in other laboratories, and generalize their application. METHODS: To evaluate this hypothesis, we aimed to develop, validate, and standardize a new measurement procedure using LC-MS/MS. Purified recombinant apoE protein standards (E2, E3, E4) were thoroughly characterized and used to assign the concentration of a matrix-matched calibration material that contained each apoE isoform, which ensured the metrological traceability of results. RESULTS: The assay of each isoform in human CSF was precise (≤11%CV) and of moderate throughput (approximately 80 samples per day). It demonstrated good linearity and parallelism for lumbar CSF, ventricular CSF, and bovine CSF. The use of an SI-traceable matrix-matched calibrator enabled precise and accurate measurements. There was no association observed between total apoE concentration and the number of Ɛ4 alleles in a cohort of 322 participants. However, the concentration of each isoform was significantly different in heterozygotes, with E4 > E3 > E2. Isoform concentrations were associated with cognitive and motor symptoms but contributed negligibly to a predictive model of cognitive impairment that included established CSF biomarkers. CONCLUSIONS: Our method simultaneously measures each apoE isoform in human CSF with excellent precision and accuracy. A secondary matrix-matched material has been developed and is available to other laboratories to improve interlaboratory agreement.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Apolipoproteína E4 / Enfermedad de Alzheimer Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: Clin Chem Asunto de la revista: QUIMICA CLINICA Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Apolipoproteína E4 / Enfermedad de Alzheimer Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: Clin Chem Asunto de la revista: QUIMICA CLINICA Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido