An accurate fully automated panel of plasma biomarkers for Alzheimer's disease

Sebastian Palmqvist, Erik Stomrud, Nicholas Cullen, Shorena Janelidze, Ekaterina Manuilova, Alexander Jethwa, Tobias Bittner, Udo Eichenlaub, Ivonne Suridjan, Gwendlyn Kollmorgen, Matthias Riepe, Christine A.F. von Arnim, Hayrettin Tumani, Klaus Hager, Fedor Heidenreich, Niklas Mattsson-Carlgren, Henrik Zetterberg, Kaj Blennow, Oskar Hansson

Research output: Contribution to journalArticlepeer-review

Abstract

Introduction: There is a great need for fully automated plasma assays that can measure amyloid beta (Aβ) pathology and predict future Alzheimer's disease (AD) dementia. Methods: Two cohorts (n = 920) were examined: Panel A+ (n = 32 cognitively unimpaired [CU], n = 106 mild cognitive impairment [MCI], and n = 89 AD) and BioFINDER-1 (n = 461 CU, n = 232 MCI). Plasma Aβ42/Aβ40, phosphorylated tau (p-tau)181, two p-tau217 variants, ApoE4 protein, neurofilament light, and GFAP were measured using Elecsys prototype immunoassays. Results: The best biomarker for discriminating Aβ-positive versus Aβ-negative participants was Aβ42/Aβ40 (are under the curve [AUC] 0.83–0.87). Combining Aβ42/Aβ40, p-tau181, and ApoE4 improved the AUCs significantly (0.90 to 0.93; P< 0.01). Adding additional biomarkers had marginal effects (ΔAUC ≤0.01). In BioFINDER, p-tau181, p-tau217, and ApoE4 predicted AD dementia within 6 years in CU (AUC 0.88) and p-tau181, p-tau217, and Aβ42/Aβ40 in MCI (AUC 0.87). Discussion: The high accuracies for Aβ pathology and future AD dementia using fully automated instruments are promising for implementing plasma biomarkers in clinical trials and clinical routine.

Original languageEnglish
JournalAlzheimer's and Dementia
DOIs
Publication statusAccepted/In press - 2022

Subject classification (UKÄ)

  • Neurosciences

Keywords

  • Alzheimer's disease
  • amyloid beta
  • apolipoprotein E
  • area under the curve
  • blood
  • cerebrospinal fluid
  • clinical practice
  • cognitively unimpaired
  • diagnostics
  • Elecsys
  • fully automated instruments
  • glial fibrillary acidic protein
  • immunoassays
  • implementation
  • mild cognitive impairment
  • neurofilament light
  • phosphorylated tau
  • plasma
  • prediction
  • prognostics

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