CSF biomarkers of Alzheimer's disease concord with amyloid-β PET and predict clinical progression: A study of fully automated immunoassays in BioFINDER and ADNI cohorts

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Abstract

Introduction: We studied whether fully automated Elecsys cerebrospinal fluid (CSF) immunoassay results were concordant with positron emission tomography (PET) and predicted clinical progression, even with cutoffs established in an independent cohort. Methods: Cutoffs for Elecsys amyloid-β1–42 (Aβ), total tau/Aβ(1–42), and phosphorylated tau/Aβ(1–42) were defined against [18F]flutemetamol PET in Swedish BioFINDER (n = 277) and validated against [18F]florbetapir PET in Alzheimer's Disease Neuroimaging Initiative (n = 646). Clinical progression in patients with mild cognitive impairment (n = 619) was studied. Results: CSF total tau/Aβ(1–42) and phosphorylated tau/Aβ(1–42) ratios were highly concordant with PET classification in BioFINDER (overall percent agreement: 90%; area under the curve: 94%). The CSF biomarker statuses established by predefined cutoffs were highly concordant with PET classification in Alzheimer's Disease Neuroimaging Initiative (overall percent agreement: 89%–90%; area under the curves: 96%) and predicted greater 2-year clinical decline in patients with mild cognitive impairment. Strikingly, tau/Aβ ratios were as accurate as semiquantitative PET image assessment in predicting visual read–based outcomes. Discussion: Elecsys CSF biomarker assays may provide reliable alternatives to PET in Alzheimer's disease diagnosis.

Detaljer

Författare
  • Oskar Hansson
  • John Seibyl
  • Erik Stomrud
  • Henrik Zetterberg
  • John Q. Trojanowski
  • Tobias Bittner
  • Valeria Lifke
  • Veronika Corradini
  • Udo Eichenlaub
  • Richard Batrla
  • Katharina Buck
  • Katharina Zink
  • Christina Rabe
  • Kaj Blennow
  • Leslie M. Shaw
  • Swedish BioFINDER study group
  • Alzheimer's Disease Neuroimaging Initiative
Enheter & grupper
Externa organisationer
  • Skåne University Hospital
  • Sahlgrenska University Hospital
  • University College London
  • Göteborgs universitet
  • UK Dementia Research Institute
  • Roche Diagnostics
  • University of Pennsylvania
  • Institute For Neurodegenerative Disorders
  • Roche Diagnostics International
Forskningsområden

Ämnesklassifikation (UKÄ) – OBLIGATORISK

  • Neurologi

Nyckelord

Originalspråkengelska
Sidor (från-till)1470-1481
TidskriftAlzheimer's and Dementia
Volym14
Utgivningsnummer11
Tidigt onlinedatum2018 feb 27
StatusPublished - 2018 nov
PublikationskategoriForskning
Peer review utfördJa