Concordance of Lumipulse cerebrospinal fluid t-tau/Aβ42 ratio with amyloid PET status

Alzheimers Dement. 2020 Jan;16(1):144-152. doi: 10.1002/alz.12000.

Abstract

Introduction: Cerebrospinal fluid (CSF) biomarkers can identify individuals with Alzheimer's disease (AD) pathology (eg, amyloid plaques, neurofibrillary tangles), but defined analyte cut-points using high-throughput automated assays are necessary for general clinical use.

Methods: CSF amyloid β42 peptide (Aβ42), t-tau, and t-tau/Aβ42 were quantified by the Lumipulse platform in two test cohorts (A/B: Eisai BAN2401-201/MISSION AD E2609-301/302, n = 138; C: Knight Alzheimer's Disease Research Center (ADRC), n = 198), and receiver operating characteristic (ROC) curve analyses defined cut-points corresponding best to amyloid determinations using positron emission tomography (PET) imaging. The best-performing cut-point was then validated as a predictor of amyloid status in an independent cohort (D: MISSION AD E2609-301/302, n = 240).

Results: Virtually identical t-tau/Aβ42 cut-points (∼0.54) performed best in both test cohorts and with similar accuracy (areas under ROC curve [AUCs] [A/B: 0.95; C: 0.94]). The cut-point yielded an overall percent agreement with amyloid PET of 85.0% in validation cohort D.

Discussion: Lumipulse CSF biomarker measures with validated cut-points have clinical utility in identifying AD pathology.

Keywords: Alzheimer's disease; Lumipulse; amyloid PET; assay validation; biomarker; cerebrospinal fluid; cut-point; t-tau/Aβ42 ratio.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Validation Study

MeSH terms

  • Aged
  • Alzheimer Disease / cerebrospinal fluid*
  • Amyloid / metabolism*
  • Amyloid beta-Peptides / cerebrospinal fluid*
  • Amyloid beta-Peptides / metabolism
  • Biomarkers / cerebrospinal fluid*
  • Cohort Studies
  • Female
  • Humans
  • Male
  • Middle Aged
  • Peptide Fragments / cerebrospinal fluid*
  • Peptide Fragments / metabolism
  • Positron-Emission Tomography
  • Reproducibility of Results
  • tau Proteins / cerebrospinal fluid*

Substances

  • Amyloid
  • Amyloid beta-Peptides
  • Biomarkers
  • Peptide Fragments
  • amyloid beta-protein (1-42)
  • tau Proteins