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.
Original language | English |
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Pages (from-to) | 144-152 |
Number of pages | 9 |
Journal | Alzheimer's and Dementia |
Volume | 16 |
Issue number | 1 |
DOIs | |
State | Published - Jan 1 2020 |
Keywords
- Alzheimer's disease
- Lumipulse
- amyloid PET
- assay validation
- biomarker
- cerebrospinal fluid
- cut-point
- t-tau/Aβ42 ratio