Concordance between the updated Elecsys cerebrospinal fluid immunoassays and amyloid positron emission tomography for Alzheimer's disease assessment: findings from the Apollo study.

Abstract

Objectives: The Apollo study was designed to support the clinical performance verification of the adjusted cutoffs of the Elecsys^® β-Amyloid(1-42) (Aβ₄₂) cerebrospinal fluid (CSF) II, β-Amyloid(1-40) (Aβ₄₀) CSF, Phospho-Tau (181P) (pTau) CSF and Total-Tau (tTau) CSF immunoassays (Roche Diagnostics International Ltd) for measuring fresh CSF samples, and assess the concordance of the Elecsys CSF pTau/Aβ₄₂, tTau/Aβ₄₂ and Aβ₄₂/Aβ₄₀ ratios, as well as Aβ₄₂ alone, with amyloid positron emission tomography (PET) visual read status.

Methods: The primary study endpoint was to assess the concordance of the Elecsys CSF ratios and Aβ₄₂ alone with amyloid PET visual read status using fresh CSF samples collected from individuals with subjective cognitive decline or mild cognitive impairment, handled with a new routine-use pre-analytical procedure and measured with the Elecsys CSF immunoassays. The sample stability after 1- to 13-week storage at -20 °C was also investigated in an exploratory analysis.

Results: Of 108 screened individuals, 91 met the eligibility criteria, of whom 44.0 % were amyloid PET-positive and 56.0 % amyloid PET-negative. Positive percent agreement (PPA) and negative percent agreement, respectively, were 0.800 and 0.882 for pTau/Aβ₄₂, 0.775 and 0.902 for tTau/Aβ₄₂, and 0.950 and 0.824 for Aβ₄₂/Aβ₄₀. For Aβ₄₂, PPA was 0.975 and negative likelihood ratio was 0.039. Overall, 33 samples (36.3 %) were frozen at -20 °C for 1-13 weeks. All concentration recoveries were within 100 ± 10 % when stored at -20 °C for ≤8 weeks.

Conclusions: Elecsys CSF ratios and Aβ₄₂ alone may be reliable alternatives to amyloid PET for identifying amyloid positivity in clinical practice.