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CSF Biomarkers in Longitudinal Alzheimer Disease Cohorts: Pre-Analytic Challenges.
Jonaitis, Erin M; Jeffers, Beckie; VandenLangenberg, Monica; Ma, Yue; Van Hulle, Carol; Langhough, Rebecca; Du, Lianlian; Chin, Nathaniel A; Przybelski, Robert J; Hogan, Kirk J; Christian, Bradley T; Betthauser, Tobey J; Okonkwo, Ozioma C; Bendlin, Barbara B; Asthana, Sanjay; Carlsson, Cynthia M; Johnson, Sterling C.
Afiliación
  • Jonaitis EM; Wisconsin Alzheimer's Institute, School of Medicine and Public Health, University of Wisconsin -Madison, Madison, WI, United States.
  • Jeffers B; Wisconsin Alzheimer's Disease Research Center, School of Medicine and Public Health, University of Wisconsin -Madison, Madison, WI, United States.
  • VandenLangenberg M; Department of Medicine, Division of Geriatrics and Gerontology, School of Medicine and Public Health, University of Wisconsin -Madison, Madison, WI, United States.
  • Ma Y; Wisconsin Alzheimer's Institute, School of Medicine and Public Health, University of Wisconsin -Madison, Madison, WI, United States.
  • Van Hulle C; Wisconsin Alzheimer's Disease Research Center, School of Medicine and Public Health, University of Wisconsin -Madison, Madison, WI, United States.
  • Langhough R; Department of Medicine, Division of Geriatrics and Gerontology, School of Medicine and Public Health, University of Wisconsin -Madison, Madison, WI, United States.
  • Du L; Wisconsin Alzheimer's Disease Research Center, School of Medicine and Public Health, University of Wisconsin -Madison, Madison, WI, United States.
  • Chin NA; Department of Medicine, Division of Geriatrics and Gerontology, School of Medicine and Public Health, University of Wisconsin -Madison, Madison, WI, United States.
  • Przybelski RJ; Wisconsin Alzheimer's Disease Research Center, School of Medicine and Public Health, University of Wisconsin -Madison, Madison, WI, United States.
  • Hogan KJ; Wisconsin Alzheimer's Disease Research Center, School of Medicine and Public Health, University of Wisconsin -Madison, Madison, WI, United States.
  • Christian BT; Wisconsin Alzheimer's Institute, School of Medicine and Public Health, University of Wisconsin -Madison, Madison, WI, United States.
  • Betthauser TJ; Wisconsin Alzheimer's Disease Research Center, School of Medicine and Public Health, University of Wisconsin -Madison, Madison, WI, United States.
  • Okonkwo OC; Department of Medicine, Division of Geriatrics and Gerontology, School of Medicine and Public Health, University of Wisconsin -Madison, Madison, WI, United States.
  • Bendlin BB; Wisconsin Alzheimer's Disease Research Center, School of Medicine and Public Health, University of Wisconsin -Madison, Madison, WI, United States.
  • Asthana S; Department of Biostatistics and Medical Informatics, School of Medicine and Public Health, University of Wisconsin -Madison, Madison, WI, United States.
  • Carlsson CM; Department of Medicine, Division of Geriatrics and Gerontology, School of Medicine and Public Health, University of Wisconsin -Madison, Madison, WI, United States.
  • Johnson SC; Department of Medicine, Division of Geriatrics and Gerontology, School of Medicine and Public Health, University of Wisconsin -Madison, Madison, WI, United States.
Clin Chem ; 70(3): 538-550, 2024 03 02.
Article en En | MEDLINE | ID: mdl-38431278
ABSTRACT

BACKGROUND:

The sensitivity of amyloid to pre-analytic factors complicates cerebrospinal fluid (CSF) diagnostics for Alzheimer disease. We report reliability and validity evidence for automated immunoassays from frozen and fresh CSF samples in an ongoing, single-site research program.

METHODS:

CSF samples were obtained from 2 Wisconsin cohorts (1256 measurements; 727 participants). Levels of amyloid beta 1-42 (Aß42), phosphorylated tau 181 (pTau181), and total tau (tTau) were obtained using an Elecsys cobas e 601 platform. Repeatability and fixed effects of storage tube type, extraction method, and freezing were assessed via mixed models. Concordance with amyloid positron emission tomography (PET) was investigated with 238 participants having a temporally proximal PET scan.

RESULTS:

Repeatability was high with intraclass correlation (ICC) ≥0.9, but tube type strongly affected measurements. Discriminative accuracy for PET amyloid positivity was strong across tube types (area under the curve [AUC] Aß42, 0.87; pTau181Aß42 , 0.96), although optimal thresholds differed.

CONCLUSIONS:

Under real-world conditions, the Elecsys platform had high repeatability. However, strong effects of pre-analytic factors suggest caution in drawing longitudinal inferences.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Enfermedad de Alzheimer Límite: Humans Idioma: En Revista: Clin Chem Asunto de la revista: QUIMICA CLINICA Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Enfermedad de Alzheimer Límite: Humans Idioma: En Revista: Clin Chem Asunto de la revista: QUIMICA CLINICA Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido